Ineffective haemopoiesis and apoptosis in myelodysplastic syndromes

British Journal of Haematology

Volumn 101, Issue 2, 1998, Pages 220-230

  Parker, J E ^a   Mufti, G J ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Acute myeloid leukaemia; Apoptosis; Bcl 2; Fas; Myelodysplastic syndrome

Indexed keywords

CYTOKINE; FAS ANTIGEN; PROTEIN BCL 2; PROTEIN P53; RETINOBLASTOMA PROTEIN; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA RECEPTOR;

APOPTOSIS; CANCER SURVIVAL; HEMATOPOIESIS; HUMAN; LEUKEMOGENESIS; MALIGNANT TRANSFORMATION; MYELODYSPLASTIC SYNDROME; PANCYTOPENIA; PRIORITY JOURNAL; PROGNOSIS; REFRACTORY ANEMIA; REVIEW;

ANTIGENS, CD95; APOPTOSIS; CELL CYCLE; DISEASE PROGRESSION; GENES, BCL-2; HEMATOPOIESIS; HUMANS; MYELODYSPLASTIC SYNDROMES; TRANSCRIPTION, GENETIC;

EID: 0031863816     PISSN: 00071048     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2141.1998.00708.x     Document Type: Review

References (108)

1. Arends, M.J. & Wyllie, A.H. (1991) Apoptosis: mechanisms and roles in pathology. International Reviews of Experimental Pathology. 32, 223-254.
2. Banner, D.W., D'Arcy, A., Janes, W., Gentz, R., Schoenfeld, H.J., Broger, C., Loetscher, H. & Lesslauer, W. (1993) Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell. 73, 431-435.
3. Barak, Y., Juven, T., Haffner, R. & Oren, M. (1993) mdm2 expression is induced by wild type p53 activity. EMBO Journal. 12, 461-468.
4. Bennett, J.M., Catovsky, D., Daniel, M.T., Flandrin, G., Galton, D.A., Gralnick, H.R. & Sultan, C. (1982) Proposals for the classification of the myelodysplastic syndromes. British Journal of Haematology. 51, 189-199.
5. Ben-Yehuda, D., Krichevsky, S., Caspi, O., Rund, D., Polliack, A., Abeliovich, D., Zelig, O., Yahalom, V., Paltiel, O., Or, R., Peretz, T., Ben-Neriah, S., Yehuda, O. & Rachmilewitz, E.A. (1996) Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype. Blood. 88, 4296-4303.
6. Bissonnette, R.P., Echeverri, F., Mahboubi, A. & Green, D.R. (1992) Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature. 359, 552-554.
7. Bogdanovic, A.D., Trpinac, D.P., Jankovic, G.M., Bumbasirevic, V.Z., Obradovic, M. & Colovic, M.D. (1997) Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment. Leukemia. 11, 656-659.
8. Boldin, M.P., Goncharov, T.M., Goltsev, Y.V. & Wallach, D. (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 85, 803-815.
9. Bouscary, D., De Vos, J., Guesnu, M., Jondeau, K., Viguier, F., Melle, J., Picard, F., Dreyfus, F. & Fontenay-Roupie, M. (1997) Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. Leukemia. 11, 839-845.
10. Bowen, D., Yancik, S., Bennett, L., Culligan, D. & Resser, K. (1993) Serum stem cell factor concentration in patients with myelodysplastic syndromes. British Journal of Haematology. 85, 63-66.
11. Bradbury, D.A., Zhu, Y.M. & Russell, N.H. (1997) Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous growth and CD34 antigen expression. Leukemia and Lymphoma. 24, 221-228.
12. Bueso-Ramos, C.E., Yang, Y., deLeon, E., McCown, P., Stass, S.A. & Albitar, M. (1943) The human MDM-2 oncogene is overexpressed in leukemias. Blood. 82, 2617-2623.
13. Campos, L., Rouault, J.P., Sabido, O., Oriol, P., Roubi, N., Vasselon, C., Archimbaud, E., Magaud, J.P. & Guyotat, D. (1993) High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood. 81, 3091-3096.
14. Chinnaiyan, A.M., O'Rourke, K., Lane, B.R. & Dixit, V.M. (1997) Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science. 275, 1122-1126.
15. Chinnaiyan, A.M., O'Rourke, K., Tewari, M. & Dixit, V.M. (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 81, 505-512.
16. Clark, D.M. & Lampert, I.A. (1990) Apoplosis is a common histopathological finding in myelodysplasia: the correlate of ineffective haematopoiesis. Leukemia and Lymphoma. 2, 415-418.
17. Coutinho, L.H., Geary, C.G., Chang, J., Harrison, C. & Testa, N.G. (1990) Functional studies of bone marrow haemopoietic and stromal cells in the myelodysplastic syndrome (MDS). British Journal of Haematology. 75, 16-25.
18. Delia, D., Aiello, A., Soligo, D., Fontanella, E., Melani, C., Pezzella, F., Pierotti, M.A. & Della-Porta, C. (1992) bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells. Blood. 79, 1291-1298.
19. el Deiry, W.S., Tokino, T., Velculescu, V.E., Levy, D.B., Parsons, R., Trent, J.M., Lin, D., Mercer, W.E., Kinzler, K.W. & Vogelstein, B. (1993) WAFL a potential mediator of p53 tumor suppression. Cell. 75, 817-825.
20. Enari, M., Talanian, R.V. Wong, W.W. & Nagata, S. (1996) Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature. 380, 723-726.
21. Evan, G.I., Wyllie, A.M., Gilbert, C.S., Littlewood, T.D., Land, H., Brooks, M., Waters, C.M., Penn, L.Z. & Hancock, D.C. (1992) Induction of apoptosis in libroblasts by c-myc protein. Cell. 69, 119-128.
22. Fakharzadeh, S.S., Trusko, S.P. & George, D.L. (1991) Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO Journal. 10, 1565-1569.
23. Finlay, C.A. (1993) The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Molecular Cell Biology. 13, 301-306.
24. Fisher, G.H., Rosenberg, F.J., Straus, S.E., Dale, J.K., Middleton, L.A., Lin, A.Y., Strober, W. Lenardo, M.J. & Puck, J.M. (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 81, 935-946.
25. Friesen, C., Herr, L. Krammer, P.M. & Debatin, K.M. (1996) Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukaemia cells. Nature Medicine. 2, 574-577.
26. Gersuk, G.M., Yamaguchi, M., Beckham, C., Kiener, P., Anderson, J.E., Trout, T., Loken, M.R. & Deeg, H.J. (1996) A role for fas, fas-ligand and TNF-α in the dysregulation of hemalopoiesis in myelodysplastic syndrome (MDS). Blood. 88, 639a.
27. Grana, X. & Reddy, E.P. (1995) Cell cycle control in mammalian cells: role of cyclins. cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 11, 211-219.
28. Greenberg, P.L., Ginzton, N., Rajapaksa, R., Tong, C.R. & Han, J.H. (1994) Apoptosis in myelodysplastic syndrome (MDS). Blood. 84, 159a.
29. Harbour, J.W., Lai, S.L., Whang-Peng, J., Gazdar, A.F., Minna, J.D. & Kaye, F.J. (1988) Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science. 241, 353-357.
30. Harrington, E.A., Bennett, M.R., Fanidi, A. & Evan, G.I. (1994) c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO Journal. 13, 3286-3295.
31. Hatta, Y., Hirama, T., Miller, C.W. Yamada, Y., Tomonaga, M. & Koeffler, H.P. (1995) Homozygous deletions of the p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia. Blood. 85, 2699-2704.
32. Helin, K., Harlow, E. & Fattaey, A. (1993) Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Molecular Cell Biology. 13, 6501-6508.
33. Hellstrom-Lindberg, E., Kanter-Lewensohn, L. & Ost, A. (1997) Morphological changes and apoptosis in bone marrow from patients with myelodysplastic syndromes treated with granulocyte-CSF and erythropoietin. Leukemia Research. 21, 415-425.
34. Hirama, T. & Koeffler, H.P. (1995) Role of the cyclin-dependent kinase inhibitors in the development of cancer. Blood. 86, 841-854.
35. Hsu, H., Huang, J., Shu, H.B., Baichwal, V. & Goeddel, D.V. (1996) TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 4, 387-396.
36. Hsu, H., Xiong, J. & Goeddel, D.V. (1995) The TNK receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 81, 495-504.
37. Hu, Z.B., Minden, M.D. & McCulloch, E.A. (1996) Post-transcriptional regulation of bel-2 in acute myeloblastic leukemia: significance for response to chemotherapy. Leukemia. 10, 410-416.
38. Itoh, N. & Nagata, S. (1993) A novel protein domain required for apoptosis: mutational analysis of human Fas antigen. Journal of Biological Chemistry. 268, 10932-10957.
39. Jacobson, M.D., Burne, J.F., King, M.P., Miyashita, T., Reed, J.C. & Raff, M.C. (1995) Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 361, 365-369.
40. Jiang, W., Zhang, Y.J., Kahn, S.M., Hollstein, M.C., Santella, R.M., Lu, S.H., Harris, C.C., Montesano, R. & Weinstein, I.B. (1993) Altered expression of the cyclin D1 and retinoblastoma genes in human esophageal cancer. Proceedings of the National Academy of Sciences of the United States of America. 90, 9026-9030.
41. Johnson, D.G., Schwarz, J.K., Cress, W.D. & Nevins, J.R. (1993) Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature. 365, 349-352.
42. Johnson, E.M., Chen, P.L., Krachmarov, C.P., Barr, M., Kanovsky, M., Ma, Z.W. & Lee, W.H. (1995) Association of human Pur alpha with the retinoblastoma protein. Rb. regulates binding to the single-stranded DNA Pur alpha recognition element. Journal of Biological Chemistry. 270, 24352-24360.
43. Jonveaux, P., Fenaux, P., Quiquandon, I., Pignon, J.M., Lai, J.L., Loucheux-Lefebvre, M.H., Goossens, M., Bauters, F. & Berger, R. (1991) Mutations in the p53 gene in myelodysplastic syndromes. Oncogene. 6, 2243-2247.
44. Kato, J., Matsushime, H., Hiebert, S.W., Ewen, M.E. & Sherr, C.J. (1993) Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes and Development. 7, 331-342.
45. Kitagawa, M., Yoshida, S., Kuwata, T. Tanizawa, T. & Kamiyama, R. (1994) p53 expression in myeloid cells of myelodysplastic syndromes: association with evolution of overt leukemia. American Journal of Pathology. 145, 338-344.
46. Kornblau, S.M., Xu, H.J., Zhang, W., Hu, S.X., Beran, M., Smith, T.L., Hester, J., Esley, E., Benedict, W.F. & Deisseroth, A.B. (1994) Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia. Blood. 84, 256-261.
47. Kuhl, J.S., Krajewski, S., Duran, G.E., Reed, J.C. & Sikic, B.I. (1997) Spontaneous overexpression of the long form of the bcl-X protein in a highly resistant P388 leukaemia. British Journal of Cancer. 75, 268-274.
48. Lai, J.L., Preudhomme, C. Zandecki, M., Flactif, M., Vanrumbeke, M., Lepelley, P., Wattel, E. & Fenaux, P. (1995) Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion: an entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. Leukemia. 9, 370-381.
49. 2+ fluxes. Proceedings of the National Academy of Sciences of the United States of America. 91, 6569-6573.
50. Landowski, T.H., Gleason-Guzman, M.C. & Dalton, W.S. (1997) Selection for drug resistance results in resistance to Fas-mediated apoptosis. Blood. 89, 1854-1861.
51. Lezon-Geyda, K.A., Najfeld, V. & Johnson, EM. (1997) Deletion of the PURA gene encoding the single-stranded DNA-binding protein PURa, in myelodysplastic syndome (MDS) and myeloid leukemias. Leukemia Research. 21, S36.
52. Lin, D., Shields, M.T., Ullrich, S.J., Appella, E. & Mercer, W.E. (1992) Growth arrest induced by wild-type p53 protein blocks cells prior to or near the restriction point in late G1 phase. Proceedings of the National Academy of Sciences of the United States of America. 89, 9210-9214.
53. Linette, G.P., Li, Y., Roth, K. & Korsmeyer, S.J. (1996) Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proceedings of the National Academy of Sciences of the United States of America. 93, 9545-9552.
54. Liu, X., Kim, C.N., Yang, J., Jemmerson, R. & Wang, X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 86, 147-157.
55. Ma, Z.W., Pejovic, T., Najfeld, V., Ward, D.C. & Johnson, E.M. (1995) Localization of PURA, the gene encoding the sequence-specific single-stranded-DNA-binding protein Pur alpha, to chromosome band 5q31. Cytogenetics and Cell Genetics. 71, 64-66.
56. + human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro. Blood. 85, 3183-3196.
57. + cells of patients with aplastic anaemia. British Journal of Haematology. 91, 245-252.
58. Marsh, J.C., Chang, J., Testa, N.G., Hows, J.M. & Dexter, T.M. (1991) In vitro assessment of marrow 'stem cell' and stromal cell function in aplastic anaemia. British Journal of Haematology. 78, 258-267.
59. Mashal, R., Shtalrid, M., Talpaz, M., Kantarjian, H., Smith, L., Beran, M., Cork, A., Trujillo, J., Gutterman, J. & Deisseroth, A. (1990) Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia. Blood. 75, 180-189.
60. Maurer, A.B., Ganser, A., Buhl, R., Seipelt, G., Ottmann, O.G., Mentzel, U., Geissler, R.G. & Hoelzer, D. (1993) Restoration of impaired cylokine secretion from monocytes of patients with myelodysplastic syndromes after in vivo treatment with GM-CSF or IL.-3. Leukemia. 7, 1728-1733.
61. Min, Y.H., Lee, S., Lee, J.W. Chong, S.Y., Hahn, J.S. & Ko, Y.W. (1996) Expression of Fas antigen in acute myeloid leukaemia is associated with therapeutic response to chemotherapy. British Journal of Haematology. 93, 928-930.
62. Minn, A.J., Velez, P., Schendel, SL., Liang, H., Muchmore, S.W. Fesik, S.W., Fill, M. & Thompson, C.B. (1997) Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature. 385, 353-357.
63. Miyashita, T., Krajewski, S., Krajewska, M., Wang, H.G., Lin, H.K., Liebermann, D.A., Hoffman, B. & Reed, J.C. (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 9, 1799-1805.
64. Muchmore, S.W., Sattler, M., Liang, H., Meadows, R.P., Harlan, J.E., Yoon, H.S., Nettesheim, D., Chang, B.S., Thompson, C.B., Wong, S.L., Ng, S.L. & Fesik, S.W. (1996) X-ray and NMR structure of human Bcl-xL. an inhibitor of programmed cell death. Nature. 381, 335-341.
65. Mufti, G.J. & Galton, D.A. (1986) Myelodysplastic syndromes: natural history and features of prognostic importance. Clinical Haematalogy. 15, 953-971.
66. Musto, P., Matera, R., Minervini, M.M., Checchia de Ambrosio, C., Bodenizza, C., Falcone, A. & Carotenuto, M. (1994) Low serum levels of tumor necrosis factor and interleukin-1 beta in myelodysplastic syndromes responsive to recombinant erythropoietin. Haematologica. 79, 265-268.
67. Muzio, M., Chinnaiyan, A.M., Kischkel, F.C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J.D., Zhang, M., Gentz, R., Mann, M., Krammer, P.H., Peter, M.E. & Dixit, V.M. (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell. 85, 817-827.
68. Nagata, S. & Golstein, P. (1995) The Fas death factor. Science. 267, 1449-1456.
69. Nakamaki, T., Bartram, C., Seriu, T., Kahan, J., Fukuchi, K., Tsuruoka, N., Janssen, J.W.G., Miller, C.W. & Koeffler, H.P. (1997) Molecular analysis of the cyclin-dependent kinase inhibitor genes, p15, p16, p18 and p19 in the myelodysplastic syndromes. Leukemia Research. 21, 235-240.
70. Nakamaki, T., Kawamata, N., Schwaller, J., Tobler, A., Fey, M., Pakkala, S., Lee, Y.Y., Kim, B.K., Fukuchi, K., Tsuruoka, N., Kahan, J., Miller, C.W. & Koeffler, H.P. (1995) Structural integrity of the cyclin-dependent kinase inhibitor genes, p15, p16 and p18 in myeloid leukaemias. British Journal of Haematology. 91, 139-149.
71. Naumovski, L. & Cleary, M.L. (1996) The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M. Molecular Cell Biology. 16, 3884-3892.
72. Oliner, J.D., Kinzler, K.W., Meltzer, P.S., George, D.I., & Vogelstein, B. (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 358, 80-83.
73. Oltvai, X.N., Milliman, C.L. & Korsmeyer, S.J. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog. Bax, that accelerates programmed cell death. Cell. 74, 609-619.
74. Owen-Schaub, L.B., Zhang, W., Cusack, J.C., Angelo, L.S., Santee, S.M., Fujiwara, T., Roth, J.A., Deisseroth, A.B., Zhang, W.W. Kruzel, E. & Radinsky, R. (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Molecular Cell Biology. 15, 3032-3040.
75. Paquette, R.L., Landaw, E.M., Pierre, R.V., Kahan, J., Lubbert, M., Lazcano, O., Isaac, G., McCormick, F. & Koeffler, H.P. (1993) N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome. Blood. 82, 590-599.
76. Parker, J.E., Fishlock, K.L., Mijovic, A., Pagliuca, A. & Mufti., G.J. (1997) Leukemic progression in myelodysplastic syndromes (MDS) is associated with decreased apoptosis and a reduced ratio of pro- versus anti-apoptotic Bcl-2 related proteins. Blood. 90, 520a.
77. Ponce-Castaneda, M.V., Lee, M.H., Latres, E., Polyak, K., Lacombe, L., Montgomery, K., Mathew, S., Krauter, K., Sheinfeld, J., Massague, J. & Cordoncardo, C. (1995) p27Kipl: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors. Cancer Research. 55, 1211-1214.
78. Preudhomme, C., Quesnel, B., Vachee, A., Lapelley, P., Collyn D'Hooghe, M., Wattel, E. & Fenaux, P. (1993) Absence of amplification of MDM2 gene, a regulator of p53 function, in myelodysplastic syndromes. Leukemia. 7, 1291-1293.
79. Preudhomme, C., Vachee, A., Lapelley, P., Vanrumbeke, M., Zandecki, M., Quesnel, B., Cosson, A. & Fenaux, P. (1994) Inactivation of the retinoblastoma gene appears to be very uncommon in myelodysplastic syndromes. British Journal of Haematology. 87, 61-67.
80. Quesnel, B., Preudhomme, C., Oscier, D., Lepelley, P., Collyn d'Hooghe, M., Facon, T., Zandecki, M. & Fenaux, P. (1994) Overexpression of the MDM2 gene is found in some cases of haematological malignancies. British Journal of Haematology. 88, 415-418.
81. Rajapaksa, R., Ginzton, N., Rott, L.S. & Greenberg, P.L. (1996) Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells. Blood. 88, 4275-4287.
82. Raza, A., Gezer, S., Gregory, S.A., Venugopal, P., Kaizer, H., Dong, L.M., Span, L. Hines, C., Thomas, R., Alvi, S., Mundle, S.D., Shetty, V., Borok, R., Loew, J., Reza, S., Robin, E.L., Rifkin, S.D., Alston, D., Hernandez, B.M., Shah, R., Hsu, W.T., Dar, S. & Preisler, H.D. (1996a) Anti-cytokine therapy produces responses in patients with myelodysplastic syndromes (MDS). Blood. 88, 580a.
83. Raza, A., Gezer, S., Mundle, S., Gao, X.Z., Alvi, S., Borok, R., Rifkin, S., Iftikhar, A., Shetty, V. Parcharidou, A., Loew, J., Marcus, B., Khan, Z., Chaney, C., Showel, J., Gregory, S. & Preisler, H. (1995) Apoplosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplaslic syndromes. Blood. 86, 268-276.
84. Raza, A., Mundle, S., Shetty, V., Alvi, S., Chopra, H., Span, L., Parcharidou, A., Dar, S., Venugopal, P., Borok, R., Gezer, S., Showel, J., Loew, J., Robin, E., Rifkin, S., Alston, D., Hernandez, B., Shah, R., Kaizer, H. & Gregory, S. (1996b) Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines. International Journal of Hematology. 63, 265-278.
85. Reed, J.C. (1997) Double identity for proteins of the Bcl-2 family. Nature. 387, 773-776.
86. Rieux-Laucat, F., Le Deist, F., Hivroz, C., Roberts, I.A., Debatin, K.M., Fischer, A. & de Villartay, J.P. (1995) Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science. 268, 1347-1349.
87. Saito, M., Helin, K., Valentine, M.B., Griffith, B.B., Willman, C.L., Harlow, E. & Look, A.T. (1995) Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line. Genomics. 25, 130-138.
88. Schendel, S.L., Xie, Z.H., Montal, M.O., Matsuyama, S., Montal, M. & Reed, J.C. (1997) Channel formation by antiapoptotic protein Bcl-2. Proceedings of the National Academy of Sciences of the United States of America. 94, 5113-5118.
89. Sherr, C.J. (1993) Mammalian G1 cyclins. Cell. 73, 1059-1065.
90. Shibasaki, F., Kondo, E., Akagi, T. & McKeon, F. (1997) Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2. Nature. 386, 728-731.
91. Shibasaki, F. & McKeon, F. (1995) Calcineurin functions in Ca(2+)-activated cell death in mammalian cells. Journal of Cell Biology. 131, 735-743.
92. Shiohara, M., el Deiry, W.S., Wada, M., Nakamaki, T. Takeuchi, S., Yang, R., Chen, D.L., Vogelstein, B. & Koeffler, H.P. (1994) Absence of WAFI mutations in a variety of human malignancies. Blood. 84, 3781-3784.
93. Silverman, L.R., Zinzar, S. & Holland, J.F. (1997) Biological consequences of stromal abnormalities in the myelodysplastic syndrome (MDS): its influence on the hematopoietic dysregulation. Leukemia Research. 21, S20.
94. Stoetzer, O.J., Nussler, V., Darsow, M., Gullis, E., Pelka-Fleischer, R., Scheel, U. & Wilmanns, W. (1996) Association of bcl-2, bax, bcl-xL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia. Leukemia. 10, S18-S22.
95. Sugimoto, K., Hirano, N., Toyoshima, H., Chiba, S., Mano, H., Takaku, F., Yazaki, Y. & Hirai, H. (1993) Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Blood. 81, 3022-3026.
96. Tewari, M., Quan, L.T., O'Rourke, K., Desnoyers, S., Zeng, Z., Beidler, D.R., Poirier, G.G., Salvesen, G.S. & Dixit, V.M. (1995) Yama/ CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 81, 801-809.
97. + cells. Blood. 88, 95a.
98. Tsujimoto, Y., Cossman, J., Jaffe, E. & Croce, C.M. (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science. 228, 1440-1443.
99. Verhoef, G.E., De Schouwer, P., Ceuppens, J.L., Van Damme, J., Goossens, W. & Boogaerts, M.A. (1992) Measurement of serum cytokine levels in patients with myelodysplastic syndromes. Leukemia. 6, 1268-1272.
100. Visani, G., Zauli, G., Tosi, P., Fogli, M., Cenacchi, A., Finelli, C., Gamberi, B., Ottaviani, E., Manfoi, S. & Tura, S. (1993) Impairment of GM-CSF production in myelodysplastic syndromes. British Journal of Haematology. 84, 227-231.
101. Wang, H.G., Rapp, U.R. & Reed, J.C. (1996) Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell. 87, 629-638.
102. Wattel, E., Preudhomme, C., Hecquet, B., Vanrumbeke, M., Quesnel, B., Dervite, I., Morel, P. & Fenaux, P. (1994) p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood. 84, 3148-3157.
103. Williams, G.T., Smith, C.A., Spooncer, E., Dexter, T.M. & Taylor, D.R. (1990) Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature. 343, 76-79.
104. Yang, E. & Korsmeyer, S.J. (1996) Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood. 88, 386-401.
105. Yang, J., Liu, X., Bhalla, K., Kim, C.N., Ibrado, A.M., Cai, J., Peng, T.I., Jones, D.P. & Wang, X. (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 275, 1129-1132.
106. Yoshida, Y. (1993) Hypothesis: apoptosis may be the mechanism responsible for the premature intramedullary cell death in the myelodysplastic syndrome. Leukemia. 7, 144-146.
107. Zhu, Y.M., Bradbury, D.A., Keith, F.J. & Russell, N. (1994) Absence of retinoblastoma protein expression results in autocrine production of interleukin-6 and promotes the autonomous growth of acute myeloid leukemia blast cells. Leukemia. 8, 1982-1988.
108. Zou, H., Henzel, W.J., Liu, X.S., Lutschg, A. & Wang, X.D. (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell. 90, 405-413.