Fol. Biol. 2006, 52, 119-136
https://doi.org/10.14712/fb2006052040119
Cell Death Signalling Pathways in the Pathogenesis and Therapy of Haematologic Malignancies: Overview of Therapeutic Approaches
References
1. 2001) Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin’s lymphoma to apoptosis. Clin. Cancer Res. 7, 709-723.
, S., Emmanouilides, C., Bonavida, B. (
2. 2003) Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin’s lymphoma and multiple myeloma to chemotherapeutic drugmediated apoptosis. Clin. Cancer Res. 9, 316-326.
, S., Bonavida, B. (
3. 2005) A novel CDK inhibitor, CYC202 (R-roscovitine), overcomes the defect in p53-dependent apoptosis in B-CLL by down-regulation of genes involved in transcription regulation and survival. Blood 105, 4484-4491.
< , A. J., Austen, B., Weston, V. J., Fegan, C., MacCallum, D., Gianella-Borradori, A., Lane, D. P., Hubank, M., Powell, J. E., Wei, W., Taylor, A. M., Moss, P. A., Stankovic, T. (https://doi.org/10.1182/blood-2004-07-2713>
4. 1997) A novel antiapoptosis gene, survivin, expressed in cancer and lymphoma. Nat. Med. 3, 917-921.
< , G., Adida, C., Altieri, D. C. (https://doi.org/10.1038/nm0897-917>
5. 1998) Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J. Biol. Chem. 273, 11177-11182.
< , G., Adida, C., Sirugo, G., Altieri, D. C. (https://doi.org/10.1074/jbc.273.18.11177>
6. 2003) Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 101, 1535-1542.
< , Y., Feldman, G. M., Tosato, G. (https://doi.org/10.1182/blood-2002-07-2130>
7. 2002) Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N. Engl. J. Med. 347, 481-487.
< , J. F., Gardembas, M., Melo, J. V., Russell-Jones, R., Bain, B. J., Baxter, J., Chase, A., Chessells, J. M., Colombat, M., Dearden, C. E., Dimitrijevic, S., Mahon, F. X., Marin, D., Nikolova, Z., Olavarria, E., Silberman, S., Schultheis, B., Cross, N. C. P., Goldman, J. M. (https://doi.org/10.1056/NEJMoa020150>
8. 2003) Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood 102, 652-658.
< , J. L., Parthun, M. R., Marcucci, G., Kitada, S., Mone, A. P., Davis, M. E., Shen, T., Murphy, T., Wickham, J., Kanakry, C., Lucas, D. M., Reed, J. C., Grever, M. R., Byrd, J. C. (https://doi.org/10.1182/blood-2002-12-3794>
9. 2005) Role of tyrosine kinase inhibitors in cancer therapy. J. Pharmacol. Exp. Ther. 315, 971-979.
< , A., Scholar, E. M. (https://doi.org/10.1124/jpet.105.084145>
10. 1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J. Clin. Invest. 104, 155-162.
< , A., Pai, R. C., Fong, S., Leung, S., Lawrence, D. A., Marsters, S. A., Blackie, C., Chang, L., McMurtrey, A. E., Hebert, A., DeForge, L., Koumenis, I. L., Lewis, D., Harris, L., Bussiere, J., Koeppen, H., Shahrokh, Z., Schwall, R. H. (https://doi.org/10.1172/JCI6926>
11. 2005) Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with dexamethasone and thalidomide in relapsed multiple myeloma patients. J. Clin. Oncol. 23, 4089-4099.
< , A. Z., Goloubeva, O., Rapoport, A. P., Ratterree, B., Gahres, N., Meisenberg, B., Takebe, N., Heyman, M., Zwiebel, J., Streicher, H., Gocke, C. D., Tomic, D., Flaws, J. A., Zhang, B., Fenton, R. G. (https://doi.org/10.1200/JCO.2005.14.381>
12. 2004) Tumor necrosis factor-related apoptosisinducing ligand cooperates with anticancer drugs to overcome chemoresistance in antiapoptotic Bcl-2 family members expressing jurkat cells. Clin. Cancer Res. 10, 1463-1470.
< , A., Nencioni, A., Boy, D., Rocco, I., Garuti, A., Mela, G. S., Van Parijs, L., Brossart, P., Wesselborg, S., Patrone, F. (https://doi.org/10.1158/1078-0432.CCR-1365-02>
13. 2002) Involvement of protein kinase C and phosphatidylinositol 3-kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells. Blood 99, 2969-2976.
< , M., Bellosillo, B., Campas, C., Colomer, D., Pons, G., Gil, J. (https://doi.org/10.1182/blood.V99.8.2969>
14. 2003) STAT1 mediates differentiation of chronic lymphocytic leukemia cells in response to Bryostatin 1. Blood 102, 3016-3024.
< , T. E., Frank, D. A. (https://doi.org/10.1182/blood-2002-09-2972>
15. 2001) Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL. Oncogene 20, 2190-2196.
< , C., Schmid, B., Marini, P., Durand, E., Rudner, J., Faltin, H., Bamberg, M., Schulze-Osthoff, K., Budach, W. (https://doi.org/10.1038/sj.onc.1204318>
16. 2003) Signal transducer and activator of transcription proteins in leukemias. Blood 101, 2940-2954.
< , M., Baer, M. R., Baumann, H., Wetzler, M. (https://doi.org/10.1182/blood-2002-04-1204>
17. 2006) Key cancer cell signal transduction pathways as therapeutic targets. Eur. J. Cancer 42, 290-294.
< , R., Melisi, D., Ciardiello, F., Tortora, G. (https://doi.org/10.1016/j.ejca.2005.07.034>
18. 2002) Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs. Leukemia 16, 455-462.
< , M. V. (https://doi.org/10.1038/sj.leu.2402415>
19. 2001) Oncogenic kinase signalling. Nature 411, 355-365.
< , P., Hunter, T. (https://doi.org/10.1038/35077225>
20. 2005) TRAIL decoy receptors mediate resistance of acute myeloid leukemia cells to TRAIL. Haematologica 90, 579.
, O. (
21. 2005) Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia. Cancer 104, 2717-2725.
< , G., Ritter, M., Wassmann, B., Schoch, C., Heinzel, T., Schwarz, K., Romanski, A., Kramer, O. H., Kampfmann, M., Hoelzer, D., Neubauer, A., Ruthardt, M., Ottmann, O. G. (https://doi.org/10.1002/cncr.21589>
22. 2003) Pyridoxal isonicotinoyl hydrazone analogs induce apoptosis in hematopoietic cells due to their iron-chelating properties. Biochem. Pharmacol. 65, 161-172.
< , J. L., Neuzil, J., Gellert, N., Weber, C., Ponka, P. (https://doi.org/10.1016/S0006-2952(02)01512-5>
23. 2004) Iron chelators in cancer chemotherapy. Curr. Top. Med. Chem. 4, 1623-1635.
< , J. L., Greene, B. T., Turner, J., Torti, F. M., Torti, S. V. (https://doi.org/10.2174/1568026043387269>
24. 2005) A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 105, 959-967.
< , J. C., Marcucci, G., Parthun, M. R., Xiao, J. J., Klisovic, R. B., Moran, M., Lin, T. S., Liu, S., Sklenar, A. R., Davis, M. E., Lucas, D. M., Fischer, B., Shank, R., Tejaswi, S. L., Binkley, P., Wright, J., Chan, K. K., Grever, M. R. (https://doi.org/10.1182/blood-2004-05-1693>
25. 2005) Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma. Cytokine 31, 368-374.
< , S., Serlupi-Crescenzi, O., Arseni, B., Rossi, S., Saggio, I., Salone, B., Cherubini, G., Carminati, P., De Santis, R. (https://doi.org/10.1016/j.cyto.2005.06.006>
26. 2005) Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood 105, 4043-4050.
< , B. Z., Gronda, M., Wang, Z., Welsh, K., Pinilla, C., Andreeff, M., Schober, W. D., Nefzi, A., Pond, G. R., Mawji, I. A., Houghten, R. A., Ostresh, J., Brandwein, J., Minden, M. D., Schuh, A. C., Wells, R. A., Messner, H., Chun, K., Reed, J. C., Schimmer, A. D. (https://doi.org/10.1182/blood-2004-08-3168>
27. 2005) ZAP-70 is a novel conditional heat shock protein 90 (Hsp90) client: inhibition of Hsp90 leads to ZAP-70 degradation, apoptosis, and impaired signaling in chronic lymphocytic leukemia. Blood 106, 2506-2512.
< , J. E., Prada, C. E., Loria, O., Kamal, A., Chen, L., Burrows, F. J., Kipps, T. J. (https://doi.org/10.1182/blood-2005-03-1099>
28. 2004) The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance. Blood 103, 3158-3166.
< , D., Li, G., Podar, K., Hideshima, T., Shringarpure, R., Catley, L., Mitsiades, C., Munshi, N., Tai, Y. T., Suh, N., Gribble, G. W., Honda, T., Schlossman, R., Richardson, P., Sporn, M. B., Anderson, K. C. (https://doi.org/10.1182/blood-2003-08-2873>
29. 2005) Proteasome inhibitor therapy in multiple myeloma. Mol. Cancer Ther. 4, 686-692.
< , D., Hideshima, T., Mitsiades, C., Richardson, P., Anderson, K. C. (https://doi.org/10.1158/1535-7163.MCT-04-0338>
30. 2004) PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Proc. Natl. Acad. Sci. USA 101, 14479-14484.
< , J., DeAngelo, D. J., Kutok, J. L., Williams, I. R., Lee, B. H., Wadleigh, M., Duclos, N., Cohen, S., Adelsperger, J., Okabe, R., Coburn, A., Galinsky, I., Huntly, B., Cohen, P. S., Meyer, T., Fabbro, D., Roesel, J., Banerji, L., Griffin, J. D., Xiao, S., Fletcher, J. A., Stone, R. M., Gilliland, D. G. (https://doi.org/10.1073/pnas.0404438101>
31. 2005) Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood 106, 2513-2519.
< , R., Keating, M. J., Gandhi, V., Plunkett, W. (https://doi.org/10.1182/blood-2005-04-1678>
32. 1998) Stabilization and activation of p53 are regulated independently by different phosphorylation events. Proc. Natl. Acad. Sci. USA 95, 2284-2289.
< , M. V., Ramana, C. V., Adler, V. V., Stark, G. R. (https://doi.org/10.1073/pnas.95.5.2284>
33. 2005) Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res. 25, 2055-2063.
, S. A., Kishino, K., Satoh, R., Hashimoto, K., Kikuchi, H., Nishikawa, H., Shirataki, Y., Sakagami, H. (
34. 2002) In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis. Blood 99, 1594-1601.
< , Y. E., Bouscary, D., Dupont, J. M., Picard, F., Melle, J., Gisselbrecht, S., Lacombe, C., Dreyfus, F., Mayeux, P., Fontenay-Roupie, M. (https://doi.org/10.1182/blood.V99.5.1594>
35. 2003a) A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N. Engl. J. Med. 348, 1201-1214.
< , J., DeAngelo, D. J., Gotlib, J., Stover, E. H., Legare, R. D., Cortes, J., Kutok, J., Clark, J., Galinsky, I., Griffin, J. D., Cross, N. C. P., Tefferi, A., Malone, J., Alam, R., Schrier, S. L., Schmid, J., Rose, M., Vandenberghe, P., Verhoef, G., Boogaerts, M., Wlodarska, I., Kantarjian, H., Marynen, P., Coutre, S. E., Stone, R., Gilliland, D. G. (https://doi.org/10.1056/NEJMoa025217>
36. 2003b) PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRα-induced myeloproliferative disease. Cancer Cell 3, 459-469.
< , J., Stover, E. H., Boulton, C. L., Gotlib, J., Legare, R. D., Amaral, S. M., Curley, D. P., Duclos, N., Rowan, R., Kutok, J. L., Lee, B. H., Williams, I. R., Coutre, S. E., Stone, R. M., DeAngelo, D. J., Marynen, P., Manley, P. W., Meyer, T., Fabbro, D., Neuberg, D., Weisberg, E., Griffin, J. D., Gilliland, D. G. (https://doi.org/10.1016/S1535-6108(03)00108-9>
37. 2003) Efficacy of the farnesyl transferase inhibitor R115777 in chronic Vol. 52 myeloid leukemia and other hematologic malignancies. Blood 101, 1692-1697.
< , J., Albitar, M., Thomas, D., Giles, F., Kurzrock, R., Thibault, A., Rackoff, W., Koller, C., O’Brien, S., GarciaManero, G., Talpaz, M., Kantarjian, H. (https://doi.org/10.1182/blood-2002-07-1973>
38. 2005) Blockage of cyclin cdk’s, PKC and phosphoinositol 3-kinase pathways leads to augmentation of apoptosis in drug-resistant leukemia cells: evidence for interactive effects of flavopiridol, LY 294002, roscovitine, wortmannin and UCN-01. Anticancer Res. 25, 101-106.
, A. H., Somerville, L., Cory, J. G. (
39. 1994) Antisense oligonucleotides suppress B-cell lymphoma growth in a Scid-hu mouse model. Oncogene 9, 3049-3055.
, F. E., Johnson, P., Hall, P., Pocock, C., Almahdi, N., Cowell, J. K., Morgan, G. (
40. 2001) Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. Cancer Res. 61, 5106-5115.
, Y., Yu, C., Singh, V., Tang, L., Wang, Z., McInistry, R., Dent, P., Grant, S. (
41. 2005) Farnesyltransferase inhibitors interact synergistically with the Chk1 inhibitor UCN-01 to induce apoptosis in human leukemia cells through interruption of both Akt and MEK/ERK pathways and activation of SEK1/JNK. Blood 105, 1706-1716.
< , Y., Rahmani, M., Pei, X. Y., Khanna, P., Han, S. I., Mitchell, C., Dent, P., Grant, S. (https://doi.org/10.1182/blood-2004-07-2767>
42. 2004) Inhibitor of apoptosis proteins: new therapeutic targets in hematological cancer? Leukemia 18, 1751-1759.
< , A. O., de Witte, T., Jansen, J. H. (https://doi.org/10.1038/sj.leu.2403493>
43. 2006) Chronic myeloproliferative disorders: a tyrosine kinase tale. Leukemia 20, 200-205.
< , K., Cools, J. (https://doi.org/10.1038/sj.leu.2404064>
44. 2000) The molecular biology of chronic myeloid leukemia. Blood 96, 3343-3356.
< , M. W. N., Goldman, J. M., Melo, J. V. (https://doi.org/10.1182/blood.V96.10.3343>
45. 2000) An overview on the use of TNF-alpha: our experience with regional administration and developments towards new opportunities for systemic application. Anticancer Res. 20, 3467-3474.
, A. H., ten Hagen, T. L., de Wilt, J. H., van Ijken, M. G., Eggermont, A. M. (
46. 2002) Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood 100, 194-199.
< , S., Monia, B., Dean, N. M., Taylor, J. K., Rapp, M. J., Harousseau, J. L., Bataille, R., Amiot, M. (https://doi.org/10.1182/blood.V100.1.194>
47. 2006) Flavopiridol in patients with relapsed or refractory multiple myeloma: a phase 2 trial with clinical and pharmacodynamic endpoints. Haematologica 91, 390-393.
, A., Gertz, M. A., Lacy, M. Q., Geyer, S. M., Fitch, T. R., Fenton, R. G., Fonseca, R., Isham, C. R., Ziesmer, S. C., Erlichman, C., Bible, K. C. (
48. 2005) BMS-354825: a novel drug with potential for the treatment of imatinib-resistant chronic myeloid leukaemia. Expert. Opin. Investig. Drugs 14, 89-91.
< , S. A. (https://doi.org/10.1517/13543784.14.1.89>
49. 1989) Bryostatin 1 induces differentiation of B-chronic lymphocytic leukemia cells. Blood 74, 1747-1757.
< , H. G., Gignac, S. M., Jones, R. A., Scott, C. S., Pettit, G. R., Hoffbrand, A. V. (https://doi.org/10.1182/blood.V74.5.1747.1747>
50. 2004) Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin’s lymphoma cells from autonomous Fas-mediated death. Proc. Natl. Acad. Sci. USA 101, 6611-6616.
< , A., O’Neil, J. D., Milner, A. E., Reynolds, G. M., Starczynski, J., Crocker, J., Young, L. S., Murray, P. G. (https://doi.org/10.1073/pnas.0400765101>
51. 1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J. Biol. Chem. 273, 14363-14367.
< , J. G., McDonnell, P., Burke, M. B., Deen, K. C., Lyn, S., Silverman, C., Dul, E., Appelbaum, E. R., Eichman, C., DiPrinzio, R., Dodds, R. A., James, I. E., Rosenberg, M., Lee, J. C., Young, P. R. (https://doi.org/10.1074/jbc.273.23.14363>
52. 1999) Overexpression of I kappa B alpha without inhibition of NF-kappaB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells. Blood 94, 3129-3134.
< , F., Meiser, M., Hummel, M., Demel, G., Foss, H. D., Jundt, F., Mathas, S., Krappmann, D., Scheidereit, C., Stein, H., Dorken, B. (https://doi.org/10.1182/blood.V94.9.3129>
53. 2001) Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J. Clin. Invest. 107, 351-362.
< , P. K., Liu, J. H., Catlett-Falcone, R., Turkson, J., Oshiro, M., Kothapalli, R., Li, Y., Wang, J. M., Yang-Yen, H. F., Karras, J., Jove, R., Loughran, T. P., Jr. (https://doi.org/10.1172/JCI9940>
54. 2005) AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells: interference with the Akt/NF-kappaB survival pathway. Leukemia 19, 572-579.
< , E., Lopez-Martin, E. M., Hernandez, d. C., Puig-Kroger, A., Soto-Cerrato, V., Montaner, B., Giralt, E., Garcia-Marco, J. A., Perez-Tomas, R., Garcia-Pardo, A. (https://doi.org/10.1038/sj.leu.2403679>
55. 1999) The clinical significance of Fas expression in leukemia: questions and controversies. Leukemia 13, 147-149.
< , H. W., Zhou, M. (https://doi.org/10.1038/sj.leu.2401280>
56. 2001) Antisense therapeutics: lessons from early clinical trials. Curr. Opin. Oncol. 13, 499-505.
< , K. T., Stevenson, J. P., O’Dwyer, P. J. (https://doi.org/10.1097/00001622-200111000-00013>
57. 2003) The phosphoinositide (PI) 3-kinase family. J. Cell. Sci. 116, 3037-3040.
< , F. M., Traer, C. J., Abraham, S. M., Fry, M. J. (https://doi.org/10.1242/jcs.00609>
58. 2003) The proteasome inhibitor PS-341 inhibits growth and induces apoptosis in Bcr/Abl-positive cell lines sensitive and resistant to imatinib mesylate. Haematologica 88, 853-863.
, S., Scappini, B., Pham, L., Onida, F., Milella, M., Ball, G., Ricci, C., Divoky, V., Verstovsek, S., Kantarjian, H. M., Keating, M. J., Cortes-Franco, J. E., Beran, M. (
59. 2001) Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins. J. Natl. Cancer Inst. 93, 463-471.
< , O., Tschopp, S., Olie, R. A., Leech, S. H., SimoesWust, A. P., Ziegler, A., Baumann, B., Odermatt, B., Hall, J., Stahel, R. A., Zangemeister-Wittke, U. (https://doi.org/10.1093/jnci/93.6.463>
60. 2003) δBAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF. J. Biol. Chem. 278, 38220-38228.
< , A. L., Ait-Azzouzene, D., Ware, C. F., Nemazee, D. (https://doi.org/10.1074/jbc.M306852200>
61. 2005) Mammalian target of rapamycin as a therapeutic target in leukemia. Curr. Mol. Med. 5, 653-661.
< , F. J., Albitar, M. (https://doi.org/10.2174/156652405774641034>
62. 2002) The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1. Clin. Cancer Res. 8, 3527-3538.
, I., Zhang, B., Fenton, R. G. (
63. 2003) Chronic myeloid leukemia – advances in biology and new approaches to treatment. N. Engl. J. Med. 349, 1451-1464.
< , J. M., Melo, J. V. (https://doi.org/10.1056/NEJMra020777>
64. 2002) BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90. Blood 100, 3041-3044.
< , M. E., Ellwood-Yen, K., Chiosis, G., Rosen, N., Sawyers, C. L. (https://doi.org/10.1182/blood-2002-05-1361>
65. 2003) Tracking death dealing by Fas and TRAIL in lymphatic neoplastic disorders: pathways, targets, and therapeutic tools. J. Leukoc. Biol. 74, 311-330.
< , R., Anether, G., Johrer, K., Tinhofer, I. (https://doi.org/10.1189/jlb.0802416>
66. 2003) Fas ligand is not constitutively expressed in low-grade B-cell lymphoma and B-lymphoblastoid cells. Eur. J. Haematol. 71, 184-188.
< , C., Richter, M., Exner, S., Finke, J. (https://doi.org/10.1034/j.1600-0609.2003.00117.x>
67. 2005) Mechanistic role of heat shock protein 70 in Bcr-Abl-mediated resistance to apoptosis in human acute leukemia cells. Blood 105, 1246-1255.
< , F., Sigua, C., Bali, P., George, P., Fiskus, W., Scuto, A., Annavarapu, S., Mouttaki, A., Sondarva, G., Wei, S., Wu, J., Djeu, J., Bhalla, K. (https://doi.org/10.1182/blood-2004-05-2041>
68. 2005) Rapamycin and UCN-01 synergistically induce apoptosis in human leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JNK signal transduction pathways. Mol. Cancer Ther. 4, 457-470.
< , M., Li, W., Yu, C., Rahmani, M., Dent, P., Grant, S. (https://doi.org/10.1158/1535-7163.MCT-04-0137>
69. 2004) TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice. Cancer Res. 64, 8502-8506.
< , C., Song, J. H., Hsi, B., Lewis, J., Song, D. K., Petruk, K. C., Tyrrell, D. L., Kneteman, N. M. (https://doi.org/10.1158/0008-5472.CAN-04-2599>
70. 2005) Clinical importance of circulating and cellular expression levels of Fas and Fas ligand in pediatric patients with lymphoproliferative malignancies. Pediatr. Hematol. Oncol. 22, 247-256.
< , V., Berber, Z., Pestereli, E., Coskun, M., Yesilipek, A., Karpuzoglu, G., Yegin, O. (https://doi.org/10.1080/08880010590921621>
71. 2004) Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. J. Immunol. 172, 3268-3279.
< , B., Chadburn, A., Jou, E., Schattner, E. J., Knowles, D. M., Cerutti, A. (https://doi.org/10.4049/jimmunol.172.5.3268>
72. 1993) Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc. Natl. Acad. Sci. USA 90, 8479-8483.
< , S., Huen, D., Rowe, M., Dawson, C., Johnson, G., Rickinson, A. (https://doi.org/10.1073/pnas.90.18.8479>
73. 1990) Bcl-2 is an inner mitochondrialmembrane protein that blocks programmed cell death. Nature 348, 334-336.
< , D., Nunez, G., Milliman, C., Schreiber, R. D., Korsmeyer, S. J. (https://doi.org/10.1038/348334a0>
74. 2001) XIAP: apoptotic brake and promising therapeutic target. Apoptosis 6, 253-261.
< , M., Gibson, H., Korneluk, R. G. (https://doi.org/10.1023/A:1011379307472>
75. 2004) Antagonizing XIAP-mediated caspase-3 inhibition: Achilles’ heel of cancers? Cancer Cell 5, 1-2.
< , Y., Lu, M., Wu, H. (https://doi.org/10.1016/S1535-6108(03)00340-4>
76. 2004) Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3,12-dioxoolean-1,9dien-28-oic acid. Mol. Cancer Ther. 3, 39-45.
< , T., Nakata, Y., Kimura, F., Sato, K., Anderson, K., Motoyoshi, K., Sporn, M., Kufe, D. (https://doi.org/10.1158/1535-7163.39.3.1>
77. 2004a) Histone deacetylase inhibitors potentiate TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in lymphoid malignancies. Cell Death. Differ. 11, S193-S206.
< , S., MacFarlane, M., Harper, N., Wheat, L. M., Dyer, M. J., Cohen, G. M. (https://doi.org/10.1038/sj.cdd.4401535>
78. 2004b) CDDO induces apoptosis via the intrinsic pathway in lymphoid cells. Leukemia 18, 948-952.
< , S., Snowden, R. T., Dyer, M. J., Cohen, G. M. (https://doi.org/10.1038/sj.leu.2403328>
79. 2000) The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism. Cell Growth Differ. 11, 261-267.
, Y., Pandey, P., Place, A., Sporn, M. B., Gribble, G. W., Honda, T., Kharbanda, S., Kufe, D. (
80. 2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434, 1144-1148.
< , C., Ugo, V., Le Couedic, J. P., Staerk, J., Delhommeau, F., Lacout, C., Garcon, L., Raslova, H., Berger, R., Bennaceur-Griscelli, A., Villeval, J. L., Constantinescu, S. N., Casadevall, N., Vainchenker, W. (https://doi.org/10.1038/nature03546>
81. 2005) The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumorigenesis and targeted antitumour therapy. Cell Mol. Biol. Lett. 10, 479-498.
, A., Robak, T., Smolewski, P. (
82. 2003) Synergistic antileukemic interactions between 17-AAG and UCN-01 involve interruption of RAF/MEKand AKT-related pathways. Blood 102, 1824-1832.
< , W., Yu, C., Rahmani, M., Krystal, G., Sausville, E. A., Dent, P., Grant, S. (https://doi.org/10.1182/blood-2002-12-3785>
83. 2000) Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat. Med. 6, 564-567.
< , M., Kim, T. H., Seol, D. W., Esplen, J. E., Dorko, K., Billiar, T. R., Strom, S. C. (https://doi.org/10.1038/75045>
84. 2005) The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol. Rev. 57, 547-583.
< , D. S., Richardson, D. R. (https://doi.org/10.1124/pr.57.4.2>
85. 2005) Phase I and pharmacokinetic study of flavopiridol followed by 1-beta-D-arabinofuranosylcytosine and mitoxantrone in relapsed and refractory adult acute leukemias. Clin. Cancer Res. 11, 8403-8412.
< , J. E., Passaniti, A., Gojo, I., Kaufmann, S., Bible, K., Garimella, T. S., Greer, J., Briel, J., Smith, B. D., Gore, S. D., Tidwell, M. L., Ross, D. D., Wright, J. J., Colevas, A. D., Bauer, K. S. (https://doi.org/10.1158/1078-0432.CCR-05-1201>
86. 2003) Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res. 9, 3578-3588.
, W. K., Richon, V. M., O’Connor, O., Curley, T., MacGregor-Curtelli, B., Tong, W., Klang, M., Schwartz, L., Richardson, S., Rosa, E., Drobnjak, M., Cordon-Cordo, C., Chiao, J. H., Rifkind, R., Marks, P. A., Scher, H. (
87. 2005) Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J. Clin. Oncol. 23, 3923-3931.
< , W. K., O’Connor, O. A., Krug, L. M., Chiao, J. H., Heaney, M., Curley, T., MacGregore-Cortelli, B., Tong, W., Secrist, J. P., Schwartz, L., Richardson, S., Chu, E., Olgac, S., Marks, P. A., Scher, H., Richon, V. M. (https://doi.org/10.1200/JCO.2005.14.167>
88. 1999) Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol. Cell. Biol. 19, 5800-5810.
< , S. G., Kandel, E. S., Cross, T. K., Hay, N. (https://doi.org/10.1128/MCB.19.8.5800>
89. 2004) Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood 103, 679-688.
< , C., Cornuel, J. F., Billard, C., Tang, R., Rouillard, D., Stenou, V., Defrance, T., Ajchenbaum-Cymbalista, F., Simonin, P. Y., Feldblum, S., Kolb, J. P. (https://doi.org/10.1182/blood-2003-02-0540>
90. 2006) NF-κB and IKK as therapeutic targets in cancer. Cell Death Differ. 13, 738-747.
< , H. J., Hawke, N., Baldwin, A. S. (https://doi.org/10.1038/sj.cdd.4401877>
91. 2002) An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J. Biol. Chem. 277, 22320-22329.
< , Y., Suh, N., Sporn, M., Reed, J. C. (https://doi.org/10.1074/jbc.M202458200>
92. 2006) Cell death signalling pathways in the pathogenesis Vol. 52 and therapy of haematologic malignancies: overview of apoptotic pathways. Folia Biol. (Praha) 52, 34-44.
, P. Jr., Anděra, L, Klener, P., Nečas, E., Živný, J. (
93. 2003) Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells. Leukemia 17, 350-358.
< , M. I., Maghraby, E. A., Parthun, M. R., Guimond, M., Sklenar, A. R., Whitman, S. P., Chan, K. K., Murphy, T., Anon, J., Archer, K. J., Rush, L. J., Plass, C., Grever, M. R., Byrd, J. C., Marcucci, G. (https://doi.org/10.1038/sj.leu.2402776>
94. 2006) Protein kinase C (PKC) family in cancer progression. Cancer Lett. 235, 1-10.
< , J., Aaltonen, V., Peltonen, J. (https://doi.org/10.1016/j.canlet.2005.03.033>
95. 2002) Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia. Blood 99, 326-335.
< , M., Tsao, T., Ruvolo, P., Stiouf, I., Estrov, Z., Leysath, C. E., Zhao, S., Harris, D., Chang, S., Jackson, C. E., Munsell, M., Suh, N., Gribble, G., Honda, T., May, W. S., Sporn, M. B., Andreeff, M. (https://doi.org/10.1182/blood.V99.1.326>
96. 2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med. 352, 1779-1790.
< , R., Passamonti, F., Buser, A. S., Teo, S., Tiedt, R., Passweg, J. R., Tichelli, A., Cazzola, M., Skoda, R. C. (https://doi.org/10.1056/NEJMoa051113>
97. 2004) Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood 104, 1266-1269.
< , A., Strupp, C., Aivado, M., Bernhardt, A., Hildebrandt, B., Haas, R., Germing, U., Gattermann, N. (https://doi.org/10.1182/blood-2003-12-4333>
98. 2006) The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer 106, 112-119.
< , A., Schmid, M., Schlenk, R., Knipp, S., Hildebrandt, B., Steidl, C., Germing, U., Haas, R., Dohner, H., Gattermann, N. (https://doi.org/10.1002/cncr.21552>
99. 2004) Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J. Clin. Oncol. 22, 1287-1292.
< , R., Albitar, M., Cortes, J. E., Estey, E. H., Faderl, S. H., Garcia-Manero, G., Thomas, D. A., Giles, F. J., Ryback, M. E., Thibault, A., De Porre, P., Kantarjian, H. M. (https://doi.org/10.1200/JCO.2004.08.082>
100. 2003) Philadelphia chromosome-positive leukemias: From basic mechanisms to molecular therapeutics. Ann. Intern. Med. 138, 819-830.
< , R., Kantarjian, H. M., Druker, B. J., Talpaz, M. (https://doi.org/10.7326/0003-4819-138-10-200305200-00010>
101. 2005) In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas. Ann. Oncol. 16, 1169-1176.
< , K., Valentini, A., Lambertini, C., Taborelli, M., Rinaldi, A., Zucca, E., Catapano, C., Cavalli, F., GianellaBorradori, A., MacCallum, D. E., Bertoni, F. (https://doi.org/10.1093/annonc/mdi217>
102. 2003) Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood 102, 3880-3889.
< , J. E., Karp, J. E. (https://doi.org/10.1182/blood-2003-02-0633>
103. 2002) The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim. Biophys. Acta 1603, 31-46.
, N. T., Richardson, D. R. (
104. 2001) Increased angiogenesis and Fas-ligand expression are independent processes in acute myeloid leukemia. Leuk. Res. 25, 1067-1073.
< , J. J., Chung, I. J., Park, M. R., Ryang, D. W., Park, C. S., Kim, H. J. (https://doi.org/10.1016/S0145-2126(01)00082-0>
105. 2005) MAP kinase p38 inhibitors: Clinical results and an intimate look at their interactions with p38 alpha protein. Curr. Med. Chem. 12, 2979-2994.
< , M. R., Dominguez, C. (https://doi.org/10.2174/092986705774462914>
106. 2006) Flavopiridol disrupts STAT3/DNA interactions, attenuates STAT3-directed transcription, and combines with the Jak kinase inhibitor AG490 to achieve cytotoxic synergy. Mol. Cancer Ther. 5, 138-148.
< , Y. K., Isham, C. R., Kaufman, S. H., Bible, K. C. (https://doi.org/10.1158/1535-7163.MCT-05-0235>
107. 1998) Fas/APO-1 (CD95) expression in myelodysplastic syndromes. Leuk. Lymphoma 30, 307-312.
< , P., Grardel, N., Erny, O., Iaru, T., Obein, V., Cosson, A., Fenaux, P. (https://doi.org/10.3109/10428199809057543>
108. 2004) Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell 6, 241-249.
< , A., Sorcinelli, M. D., Beard, C., Korsmeyer, S. J. (https://doi.org/10.1016/j.ccr.2004.07.011>
109. 2005) Pharmacological manipulation of Bcl-2 family members to control cell death. J. Clin. Invest. 115, 2648-2655.
< , A. (https://doi.org/10.1172/JCI26250>
110. 2002) A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood 99, 3885-3891.
< , M., Allebach, J., Tse, K. F., Zheng, R., Baldwin, B. R., Smith, B. D., Jones-Bolin, S., Ruggeri, B., Dionne, C., Small, D. (https://doi.org/10.1182/blood.V99.11.3885>
111. 2001) Evaluation of farnesyl: protein transferase and geranylgeranyl: protein transferase inhibitor combinations in preclinical models. Cancer Res. 61, 8758-8768.
, R. B., Omer, C. A., Abrams, M. T., Bhimnathwala, H. G., Brucker, M. J., Buser, C. A., Davide, J. P., deSolms, S. J., Dinsmore, C. J., Ellis-Hutchings, M. S., Kral, A. M., Liu, D., Lumma, W. C., Machotka, S. V., Rands, E., Williams, T. M., Graham, S. L., Hartman, G. D., Oliff, A. I., Heimbrook, D. C., Kohl, N. E. (
112. 2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487-501.
< , R. M., Killeen, N., Lenardo, M. J. (https://doi.org/10.1016/S0092-8674(01)00237-9>
113. 2003) Iron chelators as anti-neoplastic agents: Current developments and promise of the PIH class of chelators. Curr. Med. Chem. 10, 1035-1049.
< , D. B., Richardson, D. R. (https://doi.org/10.2174/0929867033457557>
114. 2004) Cytokine overexpression and constitutive NF kappa B in cancer. Cell Cycle 3, 1114-1117.
, T., Stark, G. R. (
115. 2006) Sensitization of TRAIL-resistant cells by inhibition of heat shock protein 90 with low-dose geldanamycin. Mol. Cancer Ther. 5, 170-178.
< , Y., Lakshmikanthan, V., Lewis, R. W., Kumar, M. V. (https://doi.org/10.1158/1535-7163.MCT-05-0129>
116. 2005) Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1. Cancer Res. 65, 5399-5407.
< , D. E., Melville, J., Frame, S., Watt, K., Anderson, S., Gianella-Borradori, A., Lane, D. P., Green, S. R. (https://doi.org/10.1158/0008-5472.CAN-05-0233>
117. 2003) BAFF and APRIL: a tutorial on B cell survival. Annu. Rev. Immunol. 21, 231-264.
< , F., Schneider, P., Rennert, P., Browning, J. (https://doi.org/10.1146/annurev.immunol.21.120601.141152>
118. 2003) Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia. Blood 101, 425-432.
< , G., Byrd, J. C., Dai, G., Klisovic, M. I., Kourlas, P. J., Young, D. C., Cataland, S. R., Fisher, D. B., Lucas, D., Chan, K. K., Porcu, P., Lin, Z. P., Farag, S. F., Frankel, S. R., Zwiebel, J. A., Kraut, E. H., Balcerzak, S. P., Bloomfield, C. D., Grever, M. R., Caligiuri, M. A. (https://doi.org/10.1182/blood-2002-06-1899>
119. 2005) Phase I study of oblimersen sodium, an antisense to Bcl-2, in untreated older patients with acute myeloid leukemia: pharmacokinetics, pharmacodynamics, and clinical activity. J. Clin. Oncol. 23, 3404-3411.
< , G., Stock, W., Dai, G., Klisovic, R. B., Liu, S., Klisovic, M. I., Blum, W., Kefauver, C., Sher, D. A., Green, M., Moran, M., Maharry, K., Novick, S., Bloomfield, C. D., Zwiebel, J. A., Larson, R. A., Grever, M. R., Chan, K. K., Byrd, J. C. (https://doi.org/10.1200/JCO.2005.09.118>
120. 2001) Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer 1, 194-202.
< , P., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., Kelly, W. K. (https://doi.org/10.1038/35106079>
121. 2004) c-FLIP mediates resistance of Hodgkin/ReedSternberg cells to death receptor-induced apoptosis. J. Exp. Med. 199, 1041-1052.
< , S., Lietz, A., Anagnostopoulos, I., Hummel, F., Wiesner, B., Janz, M., Jundt, F., Hirsch, B., Johrens-Leder, K., Vornlocher, H. P., Bommert, K., Stein, H., Dorken, B. (https://doi.org/10.1084/jem.20031080>
122. 2003) In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia. Leukemia 17, 849-855.
< , R. A., Tefferi, A., Gray, L. A., Reeder, T., Schroeder, G., Kaufmann, S. H. (https://doi.org/10.1038/sj.leu.2402901>
123. 2005) Beyond single pathway inhibition: MEK inhibitors as a platform for the development of pharmacological combinations with synergistic anti-leukemic effects. Curr. Pharm. Des. 11, 2779-2795.
< , M., Precupanu, C. M., Gregorj, C., Riceiardi, M. R., Petrucci, M. T., Kornblau, S. M., Tafuri, A., Andreeff, M. (https://doi.org/10.2174/1381612054546842>
124. 2006) Antimyeloma activity of heat shock protein-90 inhibition. Blood 107, 1092-1100.
< , C. S., Mitsiades, N. S., McMullan, C. J., Poulaki, V., Kung, A. L., Davies, F. E., Morgan, G., Akiyama, M., Shringarpure, R., Munshi, N. C., Richardson, P. G., Hideshima, T., Chauhan, D., Gu, X., Bailey, C., Joseph, M., Libermann, T. A., Rosen, N. S., Anderson, K. C. (https://doi.org/10.1182/blood-2005-03-1158>
125. 2004) BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood 103, 3148-3157.
< , J., Legouffe, E., Jourdan, E., Quittet, P., Reme, T., Lugagne, C., Moine, P., Rossi, J. F., Klein, B., Tarte, K. (https://doi.org/10.1182/blood-2003-06-1984>
126. 2003) Regulation of map kinase signaling modules by scaffold proteins in mammals. Annu. Rev. Cell. Dev. Biol. 19, 91-118.
< , D. K., Davis, R. J. (https://doi.org/10.1146/annurev.cellbio.19.111401.091942>
127. 1999) Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer. J. Clin. Oncol. 17, 3586-3595.
< , J., Holmlund, J. T., Kraynak, M., Richards, D., Bruce, J., Ognoskie, N., Kwoh, T. J., Geary, R., Dorr, A., Von Hoff, D., Eckhardt, S. G. (https://doi.org/10.1200/JCO.1999.17.11.3586>
128. 1996) Expression of CD95 antigen and Bcl-2 protein in nonHodgkin’s lymphomas and Hodgkin’s disease. Am. J. Pathol. 148, 847-853.
, P. L., Harris, N. L., Ritz, J., Robertson, M. J. (
129. 2003) High-level expression of BCL3 differentiates t(2; 5)(p23; q35)-positive anaplastic large cell lymphoma from Hodgkin disease. Blood 101, 2789-2796.
< , M., Maesako, Y., Ueda, C., Kurata, M., Uchiyama, T., Ohno, H. (https://doi.org/10.1182/blood-2002-08-2464>
130. 2005) Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1α. Blood 106, 1012-1020.
< , M., Endo, T., Tsukada, N., Ohata, J., Kitada, S., Reed, J. C., Zvaifler, N. J., Kipps, T. J. (https://doi.org/10.1182/blood-2004-03-0889>
131. 2005) Phase I to II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in patients with advanced chronic lymphocytic leukemia. J. Clin. Oncol. 23, 7697-7702.
< , S. M., Cunningham, C. C., Golenkov, A. K., Turkina, A. G., Novick, S. C., Rai, K. R. (https://doi.org/10.1200/JCO.2005.02.4364>
132. 1993) Lethal effect of the anti-Fas antibody in mice. Nature 364, 806-809.
< , J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., Nagata, S. (https://doi.org/10.1038/364806a0>
133. 2000) Amplification and expression of a decoy receptor for fas ligand (DcR3) in virus (EBV or HTLV-I) associated lymphomas. Cancer Lett. 160, 89-97.
< , K., Haraoka, S., Sugihara, M., Suzumiya, J., Kawasaki, C., Kanda, M., Kikuchi, M. (https://doi.org/10.1016/S0304-3835(00)00567-X>
134. 1995) BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes. Blood 86, 1893-1902.
< , J. J., van den Brule, A. J., Jiwa, N. M., de Bruin, P. C., Ossenkoppele, G. J., van, d., V, Walboomers, J. M., Meijer, C. J. (https://doi.org/10.1182/blood.V86.5.1893.bloodjournal8651893>
135. 2004) Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders. Blood 104, 1931-1939.
< , A., Tefferi, A. (https://doi.org/10.1182/blood-2004-01-0246>
136. 2003) Novel mechanisms of apoptosis induced by histone deacetylase inhibitors. Cancer Res. 63, 4460-4471.
, M. J., Tainton, K. M., Ruefli, A. A., Dear, A. E., Sedelies, K. A., O’Reilly, L. A., Waterhouse, N. J., Trapani, J. A., Johnstone, R. W. (
137. 2004) Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Clin. Cancer Res. 10, 3839-3852.
< , X. Y., Dai, Y., Grant, S. (https://doi.org/10.1158/1078-0432.CCR-03-0561>
138. 2002) Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6kinase pathways in the proliferation and apoptosis in multiple myeloma. Oncogene 21, 6587-6597.
< , F., Claessens, Y. E., Muller, O., Viguie, F., Mayeux, P., Dreyfus, F., Lacombe, C., Bouscary, D. (https://doi.org/10.1038/sj.onc.1205923>
139. 2003) Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J. Immunol. 171, 88-95.
< , L. V., Tamayo, A. T., Yoshimura, L. C., Lo, P., Ford, R. J. (https://doi.org/10.4049/jimmunol.171.1.88>
140. 2002) TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors. Leukemia 16, 67-73.
< , M., Zivny, J., Jelinek, J., Neuwirtova, R., Cermak, J., Necas, E., Andera, L., Stopka, T. (https://doi.org/10.1038/sj.leu.2402338>
141. 2003) Map kinase signaling pathways and hematologic malignancies. Blood 101, 4667-4679.
< , L. C. (https://doi.org/10.1182/blood-2002-12-3647>
142. 2001) Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J. Clin. Oncol. 19, 1485-1492.
< , D. J., McDonald, A. C., Man, A., Thavasu, P., Balkwill, F., Braybrooke, J. P., Caponigro, F., Graf, P., Dutreix, C., Blackie, R., Kaye, S. B., Ganesan, T. S., Talbot, D. C., Harris, A. L., Twelves, C. (https://doi.org/10.1200/JCO.2001.19.5.1485>
143. 2005) Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica 90, 986-988.
, E., Chaibi, P., Dombret, H., Degos, L. (
144. 2002) UCN-01 (7-hydroxystaurosporine) blocks PMA-induced maturation and reciprocally promotes apoptosis in human myelomonocytic leukemia cells (U937). Cell Cycle 1, 273-281.
< , M., Grant, S. (https://doi.org/10.4161/cc.1.4.138>
145. 2005) Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. Blood 106, 1042-1047.
< , N., Kumar, S., Hideshima, T., Roccaro, A., Ishitsuka, K., Yasui, H., Shiraishi, N., Chauhan, D., Munshi, N. C., Green, S. R., Anderson, K. C. (https://doi.org/10.1182/blood-2005-01-0320>
146. 1998) Chromosomal and gene amplification in diffuse large B-cell lymphoma. Blood 92, 234-240. Vol. 52.
< , P. H., Houldsworth, J., Dyomina, K., Parsa, N. Z., Cigudosa, J. C., Louie, D. C., Popplewell, L., Offit, K., Jhanwar, S. C., Chaganti, R. S. (https://doi.org/10.1182/blood.V92.1.234.413k22_234_240>
147. 2004) Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade nonHodgkin’s lymphoma. Ann. Oncol. 15, 1413-1418.
< , S., Watkins, D., Cunningham, D., Dunlop, D., Johnson, P., Selby, P., Hancock, B. W., Fegan, C., Culligan, D., Schey, S., Morris, T. C., Lissitchkov, T., Oliver, J. W., Holmlund, J. T. (https://doi.org/10.1093/annonc/mdh359>
148. 2004) Genomic mechanisms of p210BCR-ABL signaling: induction of heat shock protein 70 through the GATA response element confers resistance to paclitaxel-induced apoptosis. J. Biol. Chem. 279, 35604-35615.
< , S., Lu, Y., Kaufmann, S. H., Gustafson, W. C., Karp, J. E., Boldogh, I., Fields, A. P., Brasier, A. R. (https://doi.org/10.1074/jbc.M401851200>
149. 2005a) Antileukemic activity of rapamycin in acute myeloid leukemia. Blood 105, 2527-2534.
< , C., Beyne-Rauzy, O., Demur, C., Chicanne, G., Dos, S. C., Mas, V. M., Benzaquen, D., Laurent, G., Huguet, F., Payrastre, B. (https://doi.org/10.1182/blood-2004-06-2494>
150. 2005b) mTOR, a new therapeutic target in acute myeloid leukemia. Cell Cycle 4, 1540-1549.
, C., Dos, S. C., Demur, C., Payrastre, B. (
151. 2005) Apoptosis-based therapies for hematologic malignancies. Blood 106, 408-418.
< , J. C., Pellecchia, M. (https://doi.org/10.1182/blood-2004-07-2761>
152. 2005) TRAIL decoy receptors mediate resistance of acute myeloid leukemia cells to TRAIL. Haematologica 90, 612-624.
, R., Pasquini, L., Mariani, G., Saulle, E., Rossini, A., Diverio, D., Pelosi, E., Vitale, A., Chierichini, A., Cedrone, M., Foa, R., Lo, C. F., Peschle, C., Testa, U. (
153. 2005) Molecular mechanisms of iron uptake by cells and the use of iron chelators for the treatment of cancer. Curr. Med. Chem. 12, 2711-2729.
< , D. R. (https://doi.org/10.2174/092986705774462996>
154. 2002) Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cδ. Blood 100, 3741-3748.
< , I., Schneller, F., Bogner, C., Hipp, S., Duyster, J., Peschel, C., Decker, T. (https://doi.org/10.1182/blood-2002-02-0539>
155. 2004) Potent antileukemic interactions between flavopiridol and TRAIL/Apo2L involve flavopiridol-mediated XIAP downregulation. Leukemia 18, 1780-1788.
< , R. R., Dai, Y., Almenara, J. A., Maggio, S. C., Grant, S. (https://doi.org/10.1038/sj.leu.2403491>
156. 2004) Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro. Leukemia 18, 1357-1363.
< , Y., Nosaka, K., Koya, Y., Yasunaga, J. I., Toyokuni, S., Matsuoka, M. (https://doi.org/10.1038/sj.leu.2403400>
157. 2005) HSP27 protects AML cells against VP-16-induced apoptosis through modulation of p38 and c-Jun. Exp. Hematol. 33, 660-670.
< , H., Geugien, M., van der, T. M., Bryantsev, A. L., Kampinga, H. H., Eggen, B. J., Vellenga, E. (https://doi.org/10.1016/j.exphem.2005.03.009>
158. 2004) Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res. 64, 7183-7190.
< , A. D. (https://doi.org/10.1158/0008-5472.CAN-04-1918>
159. 2004) Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 5, 25-35.
< , A. D., Welsh, K., Pinilla, C., Wang, Z., Krajewska, M., Bonneau, M. J., Pedersen, I. M., Kitada, S., Scott, F. L., Bailly-Maitre, B., Glinsky, G., Scudiero, D., Sausville, E., Salvesen, G., Nefzi, A., Ostresh, J. M., Houghten, R. A., Reed, J. C. (https://doi.org/10.1016/S1535-6108(03)00332-5>
160. 2006) Dasatinib (BMS354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 66, 473-481.
< , M. M., Shiraga, S., Schroeder, A., Corbin, A. S., Griffith, D., Lee, F. Y., Bokemeyer, C., Deininger, M. W., Druker, B. J., Heinrich, M. C. (https://doi.org/10.1158/0008-5472.CAN-05-2050>
161. 2003) BAFF and the regulation of B cell survival. Immunol. Lett. 88, 57-62.
< , P., Tschopp, J. (https://doi.org/10.1016/S0165-2478(03)00050-6>
162. 2002) Adhesion-mediated intracellular redistribution of c-Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein-long confers resistance to CD95induced apoptosis in hematopoietic cancer cell lines. J. Immunol. 168, 2544-2553.
< , K. H., Landowski, T. H., Dalton, W. S. (https://doi.org/10.4049/jimmunol.168.5.2544>
163. 2004) Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc. Natl. Acad. Sci. USA 101, 18030-18035.
< , Y., Gao, Z., Marks, P. A., Jiang, X. (https://doi.org/10.1073/pnas.0408345102>
164. 2004) Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin. Cancer Res. 10, 4270s-4275s.
< , G. I. (https://doi.org/10.1158/1078-0432.CCR-040020>
165. 2004) Caspase activation, inhibition, and reactivation: a mechanistic view. Protein Sci. 13, 1979-1987.
< , Y. (https://doi.org/10.1110/ps.04789804>
166. 2003) Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells. Cancer Res. 63, 912-916.
, C. M., Croucher, P. I. (
167. 1985) Fused transcript of Abl and Bcr genes in chronic myelogenous leukemia. Nature 315, 550-554.
< , E., Lifshitz, B., Gale, R. P., Canaani, E. (https://doi.org/10.1038/315550a0>
168. 1994) Structure, regulation and function of NF-κB. Annu. Rev. Cell Biol. 10, 405-455.
< , U., Franzoso, G., Brown, K. (https://doi.org/10.1146/annurev.cb.10.110194.002201>
169. 2002) Selective inhibition of FLICE-like inhibitory protein expression with small interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL-induced apoptosis. Mol. Med. 8, 725-732.
< , D., Hadwiger, P., Pfizenmaier, K., Vornlocher, H. P., Wajant, H. (https://doi.org/10.1007/BF03402036>
170. 2002) Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 99, 618-626.
< , B. F., Elia, A. J., Gascoyne, R. D., Patterson, B., Trumper, L., Kapp, U., Mak, T. W. (https://doi.org/10.1182/blood.V99.2.618>
171. 1997) Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Aktdependent pathway. EMBO J. 16, 6151-6161.
< , T., Bellacosa, A., Nieborowska-Skorska, M., Majewski, M., Martinez, R., Choi, J. K., Trotta, R., Wlodarski, P., Perrotti, D., Chan, T. O., Wasik, M. A., Tsichlis, P. N., Calabretta, B. (https://doi.org/10.1093/emboj/16.20.6151>
172. 2003) Roles of specific isoforms of protein kinase C in the transcriptional control of cyclin D1 and related genes. J. Biol. Chem. 278, 34709-34716.
< , J. W., Weinstein, I. B. (https://doi.org/10.1074/jbc.M302016200>
173. 2005) The activation of Akt/PKB signaling pathway and cell survival. J. Cell Mol. Med. 9, 59-71.
< , G., Ouyang, G., Bao, S. (https://doi.org/10.1111/j.1582-4934.2005.tb00337.x>
174. 2001) Constitutive activation of STAT transcription factors in acute myelogenous leukemia. Eur. J. Haematol. 67, 63-71.
< , K., Biethahn, S., Wilde, S., Hiddemann, W., Alves, F. (https://doi.org/10.1034/j.1600-0609.2001.t01-1-00385.x>
175. 2002) The novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) potently enhances apoptosis induced by tumor necrosis factor in human leukemia cells. J. Biol. Chem. 277, 16448-16455.
< , T. A., Suh, N., Ganju, N., Sporn, M. B., Eastman, A. (https://doi.org/10.1074/jbc.M108974200>
176. 2004) Distinctive activation mechanisms and functions for protein kinase Cδ. Biochem. J. 384, 449-459.
< , S. F. (https://doi.org/10.1042/BJ20040704>
177. 2005) Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 105, 54-60.
< , R. M., DeAngelo, D. J., Klimek, V., Galinsky, I., Estey, E., Nimer, S. D., Grandin, W., Lebwohl, D., Wang, Y., Cohen, P., Fox, E. A., Neuberg, D., Clark, J., Gilliland, D. G., Griffin, J. D. (https://doi.org/10.1182/blood-2004-03-0891>
178. 1997) Membrane Fas ligand kills human peripheral blood T lymphocytes, and soluble Fas ligand blocks the killing. J. Exp. Med. 186, 2045-2050.
< , T., Hashimoto, H., Tanaka, M., Ochi, T., Nagata, S. (https://doi.org/10.1084/jem.186.12.2045>
179. 2002) Suppression of Akt signaling induces Fas ligand expression: involvement of caspase and Jun kinase activation in Akt-mediated Fas ligand regulation. Mol. Cell Biol. 22, 680-691.
< , T., Kim, H. S., Kirshenbaum, L. A., Walsh, K. (https://doi.org/10.1128/MCB.22.2.680-691.2002>
180. 2006) Histone deacetylase inhibitor depsipeptide (FK228) induces apoptosis in leukemic cells by facilitating mitochondrial translocation of Bax, which is enhanced by the proteasome inhibitor bortezomib. Acta Haematol. 115, 78-90.
< , K., Kobayashi, Y., Takatoku, M. A., Ozawa, K., Kano, Y., Ishii, H., Furukawa, Y. (https://doi.org/10.1159/000089471>
181. 2002) Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J. Exp. Med. 195, 161-169.
< , K., Smyth, M. J., Cretney, E., Hayakawa, Y., Kayagaki, N., Yagita, H., Okumura, K. (https://doi.org/10.1084/jem.20011171>
182. 2005) Combination therapy with interleukin-6 receptor superantagonist Sant7 and dexamethasone induces antitumor effects in a novel SCID-hu in vivo model of human multiple myeloma. Clin. Cancer Res. 11, 4251-4258.
< , P., Neri, P., Burger, R., Savino, R., Shammas, M., Catley, L., Podar, K., Chauhan, D., Masciari, S., Gozzini, A., Tagliaferri, P., Venuta, S., Munshi, N. C., Anderson, K. C. (https://doi.org/10.1158/1078-0432.CCR-04-2611>
183. 2006) The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL. Blood 107, 1149-1155.
< , D. T., Obzut, D. A., Cooperman, J., Fang, J., Carroll, M., Choi, J. K., Houghton, P. J., Brown, V. I., Grupp, S. A. (https://doi.org/10.1182/blood-2005-05-1935>
184. 2002) Constitutive expression of c-FLIP in Hodgkin and Reed-Sternberg cells. Am. J. Pathol. 160, 1521-1528.
< , R. K., Kallenborn, A., Wickenhauser, C., Schultze, J. L., Draube, A., Vockerodt, M., Re, D., Diehl, V., Wolf, J. (https://doi.org/10.1016/S0002-9440(10)62578-3>
185. 2005) Heat shock proteins and acute leukemias. Hematology 10, 225-235.
< , X., Campos, L., Le, Q. H., Guyotat, D. (https://doi.org/10.1080/10245330500093120>
186. 2003) Combined targeted inhibition of bcl-2, bcl-XL, epidermal growth factor receptor, and protein kinase A type I causes potent antitumor, apoptotic, and antiangiogenic activity. Clin. Cancer Res. 9, 866-871.
, G., Caputo, R., Damiano, V., Caputo, R., Troiani, T., Veneziani, B. M., De Placido, S., Bianco, A. R., Zangemeister-Wittke, U., Ciardiello, F. (
187. 2004) Cancer. Gleevec, chapter two: new leukemia drug aims to overcome resistance. Science 305, 319-321.
< , J. (https://doi.org/10.1126/science.305.5682.319a>
188. 2004) Switching leukemia cell phenotype between life and death. Proc. Natl. Acad. Sci. USA 101, 12940-12945.
< , S. J., Rae, C., Littlejohn, A. F., Paul, A., MacEwan, D. J. (https://doi.org/10.1073/pnas.0400949101>
189. 1996) Protein kinase C activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf. J. Biol. Chem. 271, 23512-23519.
< , Y., Hirai, S., Osada, S., Suzuki, A., Mizuno, K., Ohno, S. (https://doi.org/10.1074/jbc.271.38.23512>
190. 2004) TRAIL induction by radiation in lymphoma patients. Cancer Invest. 22, 522-525.
< , J., Macklis, R. M. (https://doi.org/10.1081/CNV-200026397>
191. 2006) JAW/STAT signal transduction: Regulators and implication in hematological malignancies. Biochem. Pharmacol. 71, 713-721.
< , L., Pierre, J. (https://doi.org/10.1016/j.bcp.2005.12.017>
192. 2004) G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma. Leukemia 18, 1078-1084.
< , N. W., de Weerdt, O., Veth, G., Eurelings, M., van Stralen, E., Frankel, S. R., Hagenbeek, A., Bloem, A. C., Lokhorst, H. M. (https://doi.org/10.1038/sj.leu.2403363>
193. 2006) TNF-α in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist 11, 397-408.
< , R., ten Hagen, T. L. M., Eggermont, A. M. M. (https://doi.org/10.1634/theoncologist.11-4-397>
194. 2003a) Bryostatin 1 and UCN01 potentiate 1-β-D-arabinofuranosylcytosine-induced apoptosis in human myeloid leukemia cells through disparate mechanisms. Mol. Pharmacol. 63, 232-242.
< , S., Wang, Z., Grant, S. (https://doi.org/10.1124/mol.63.1.232>
195. 2003b) Targeting Bcl-2 and Bcl-XL with nonpeptidic small-molecule antagonists. Semin. Oncol. 30, 133-142.
< , S., Yang, D., Lippman, M. E. (https://doi.org/10.1053/j.seminoncol.2003.08.015>
196. 2004) Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitors. J. Biol. Chem. 279, 48168-48176.
< , Z., Cuddy, M., Samuel, T., Welsh, K., Schimmer, A., Hanaii, F., Houghten, R., Pinilla, C., Reed, J. C. (https://doi.org/10.1074/jbc.M405022200>
197. 2000) Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin’s lymphoma. J. Clin. Oncol. 18, 1812-1823.
< , J. S., Webb, A., Cunningham, D., Clarke, P. A., Raynaud, F., di Stefano, F., Cotter, F. E. (https://doi.org/10.1200/JCO.2000.18.9.1812>
198. 2003) Mitochondria play a central role in apoptosis induced by α-tocopheryl succinate, an agent with antineoplastic activity: comparison with receptormediated pro-apoptotic signaling. Biochemistry 42, 4277-4291.
< , T., Dalen, H., Andera, L., Negre-Salvayre, A., Auge, N., Sticha, M., Lloret, A., Terman, A., Witting, P. K., Higuchi, M., Plasilova, M., Zivny, J., Gellert, N., Weber, C., Neuzil, J. (https://doi.org/10.1021/bi020527j>
199. 2002) Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 1, 433-443.
< , E., Boulton, C., Kelly, L. M., Manley, P., Fabbro, D., Meyer, T., Gilliland, D. G., Griffin, J. D. (https://doi.org/10.1016/S1535-6108(02)00069-7>
200. 2004) The Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates the mitogen-activated protein kinase pathway. Cancer Res. 64, 262-272.
< , S. R., Walton, M. I., Garrett, M. D., Workman, P. (https://doi.org/10.1158/0008-5472.CAN-03-0110>
201. 2005) Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J. Clin. Oncol. 23, 5347-5356.
< , T. E., Geyer, S. M., Ghobrial, I., Inwards, D. J., Fonseca, R., Kurtin, P., Ansell, S. M., Luyun, R., Flynn, P. J., Morton, R. F., Dakhil, S. R., Gross, H., Kaufmann, S. H. (https://doi.org/10.1200/JCO.2005.13.466>
202. 2005) Molecular pharmacology of the interaction of anthracyclines with iron. Mol. Pharmacol. 68, 261-271.
< , X., Persson, H. L., Richardson, D. R. (https://doi.org/10.1124/mol.105.013383>
203. 2002) UCN-01 (7hydroxystaurosporine) inhibits DNA repair and increases cytotoxicity in normal lymphocytes and chronic lymphocytic leukemia lymphocytes. Mol. Cancer Ther. 1, 287-294.
, T., Keating, M. J., Plunkett, W. (
204. 2006) Tipifarnib and bortezomib are synergistic and overcome cell adhesion-mediated drug resistance in multiple myeloma and acute myeloid leukemia. Clin. Cancer Res. 12, 591-599.
< , N., Colaco, N. M., Parquet, N. A., Buzzeo, R. W., Boulware, D., Wright, G., Perez, L. E., Dalton, W. S., Beaupre, D. M. (https://doi.org/10.1158/1078-0432.CCR-05-1792>
205. 2006) Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475-482.
< , O. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., Morrison, S. J. (https://doi.org/10.1038/nature04703>
206. 2003) The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571. Blood 102, 3765-3774.
< , C., Rahmani, M., Conrad, D., Subler, M., Dent, P., Grant, S. (https://doi.org/10.1182/blood-2003-03-0737>
207. 2000) A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xL expression efficiently induces apoptosis in tumor cells. Clin. Cancer Res. 6, 2547-2555.
, U., Leech, S. H., Olie, R. A., SimoesWust, A. P., Gautschi, O., Luedke, G. H., Natt, F., Haner, R., Martin, P., Hall, J., Nalin, C. M., Stahel, R. A. (
208. 2000) Growth of FasL-bearing tumor cells in syngeneic murine host induces apoptosis and toxicity in Fas(+) organs. Blood 95, 2111-2117.
< , A., Nagarkatti, M., Nagarkatti, P. S. (https://doi.org/10.1182/blood.V95.6.2111>
209. 2004) Regulation of apoptosis proteins in cancer cells by ubiquitin. Oncogene 23, 2009-2015.
< , H. G., Wang, J., Yang, X., Hsu, H. C., Mountz, J. D. (https://doi.org/10.1038/sj.onc.1207373>