Mcl-1 and Bcl-2/Bax Ratio Are Associated with Treatment Response but Not with Rai Stage in B-Cell Chronic Lymphocytic Leukemia

American Journal of Hematology

Volumn 75, Issue 1, 2004, Pages 22-33

  Saxena, Anurag ^a   Viswanathan, Sathiyanarayanan ^a   Moshynska, Oksana ^a   Tandon, Puneeta ^b   Sankaran, Koravangattu ^a   Sheridan, David P ^a  

^a ROYAL UNIVERSITY HOSPITAL   (Canada)

^b University Hospital Edmonton   (Canada)

Author keywords

Apoptosis; Bcl 2 Bax ratio; Chronic lymphocytic leukemia; Mcl 1; Treatment response

Indexed keywords

CHLORAMBUCIL; CYCLOPHOSPHAMIDE; DOXORUBICIN; FLUDARABINE; PREDNISONE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN MCL 1; VINCRISTINE SULFATE;

ADULT; AGED; ARTICLE; B CELL LEUKEMIA; CANCER STAGING; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DRUG EFFECT; FEMALE; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TREATMENT OUTCOME; WESTERN BLOTTING;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS, ALKYLATING; ANTINEOPLASTIC AGENTS, HORMONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BCL-2-ASSOCIATED X PROTEIN; CHLORAMBUCIL; FEMALE; HUMANS; LEUKEMIA, B-CELL, CHRONIC; LEUKEMIA, LYMPHOCYTIC, CHRONIC; MALE; MIDDLE AGED; NEOPLASM PROTEINS; NEOPLASM STAGING; PREDNISONE; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-BCL-2; ROC CURVE; TREATMENT OUTCOME;

EID: 0347416908     PISSN: 03618609     EISSN: None     Source Type: Journal    
DOI: 10.1002/ajh.10453     Document Type: Article

References (74)

1. Molica S. Progression and survival studies in early chronic lymphocytic leukemia. Blood 1991;78:895-899.
2. Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P. et al. V(H) mutation status. CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002;100:1410-1416.
3. Ghia P, Guida G, Stella S, Gottardi D, Geuna M, Strola G, et al. The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Blood [online serial] 2002;October 24 (available at http://www.bloodjournal.org).
4. Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001;194:1639-1647.
5. Klein U, Tu Y, Stolovitzky GA, Mattioli M, Cattoretti G, Husson H, et al. Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogenous phenotype related to memory B-cells. J Exp Med 2001;194:1625-1638.
6. Duerig J, Nueckel H, Huettmann A, Kruse E, Hoelter T, Halfmeyer K, et al. Expression of ribosomal and translation-associated genes is correlated wit a favorable clinical course in chronic lymphocytic leukemia. Blood [online serial] 2002;November 27 (available at http://www.bloodjournal.org).
7. Kipps TJ. Chronic lymphocytic leukemia. Curr Opin Hematol 1997;4:268-276.
8. Faguet GB. Chronic lymphocytic leukemia: an updated review. J Clin Oncol 1994;12:1974-1990.
9. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996;87:4990-4997.
10. Caligaris-Cappio F. B-chronic lymphocytic leukemia: a malignancy of anti-self B cells. Blood 1996;87:2615-2620.
11. Binet JL, Plunkett W, Robertson B, Merle-Beral, Mentz F, Hoffbrand AV, et al. What does apoptosis mean in CLL? Leukemia Lymphoma 1996;22(Suppl2):47-52.
12. Aguilar-Santelises M, Rottenberg ME, Lewin N, Mellstedt H, Jondal M. Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression. Int J Cancer 1996;69:114-119.
13. Bannerji R, Byrd JC. Update on the biology of chronic lymphocytic leukemia. Curr Opin Oncol 2000;12:22-29.
14. Robertson LE, Chubb S, Meyn RE, Story M, Ford R, Hittelman WN, et al. Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2′-deoxyadenosine and 9-β-D-arabinosyl-2-fluoroadenine. Blood 1993;81:143-150.
15. Begleiter A, Lee K, Israels LG, Mowat MR, Jonhston JB. Chlorambucil-induced apoptosis in chronic lymphocytic leukemia (CLL) and its relationship to clinical efficacy. Leukemia 1994;8(Suppl 1):S103-106.
16. Osorio LM, Jondal M, Aguilar-Santelises M. Regulation of B-CLL apoptosis through membrane receptors and Bcl-2 family proteins. Leukemia Lymphoma 1998;30:247-256.
17. Adams JM. Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998;281:1322-1326.
18. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998;281:1309-1312.
19. Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899-1911.
20. Zamzami N, Brenner C, Marzo I, Susto SA, Kroemer G, Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene 1998;16:2265-2282.
21. Hsu SY, Kaipia A, McGee E, Lomeli M, Hsueh AJ. Bok is a proapoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Proc Natl Acad Sci U S A 1997;94:12401-12406.
22. Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. Bcl-2/Bax: a rheostat that regutares anti-oxidant pathway and cell death. Semin Cancer Biol 1993;4:327-332.
23. Hande S, Notidis E, Manser T. Bcl-2 obstructs negative selection of autoreactive, hypermutated antibody V regions during memory B cell development. Immunity 1998;8:189-198.
24. Lomo J, Smeland EB, Krajewski S, Reed JC, Blomhoff HK. Expression of the Bcl-2 homologue Mcl-1 correlates with survival of peripheral blood B lymphocytes. Cancer Res 1996;56:40-43.
25. Pedersen IM, Kitada S, Schimmer A, Kim Y, Zapata JM, Charboneau L, et al. The triterpenoid CDDO induces apoptosis in refractory B cells. Blood 2002;100(8):2965-2972.
26. Pepper C, Bentley P, Hoy T. Regulation of clinical chemoresistance by bcl-2 and bax oncoproteins in B-cell chronic lymphocytic leukemia. Br J Haematol 1996;95:513-517.
27. Thomas A, El Rouby S, Reed JC, Krajewski S, Silber R, Potmesil M, et al. Drug induced apoptosis in B-cell chronic lymphocytic leukemia: relationship between p53 gene mutation and bcl-2/bax proteins in drug resistance. Oncogene 1996;12:1055-1062.
28. Pepper C, Hoy T, Bentley DP. Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance. Br J Cancer 1997;76:935-938.
29. Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood 1998;91:3379-3389.
30. Johnston JB, Daeninck P, Verburg L, Lee K, Williams G, Israels LG, et al. P53, MDM-2. BAX and BCL-2 and drug resistance in chronic lymphocytic leukemia. Leuk Lymphoma 1997;26:435-449.
31. Bellosillo B, Villamor N, Colomer D, Pons G, Montserrat E, Gil J. In vitro evaluation of fludarabine in combination with cyclophosphamide and/or mitoxantrone in B-cell chronic lymphocytic leukemia. Blood 1999;94:2836-2843.
32. Pepper C, Thomas A, Hoy T, Fegan C, Bentley P. Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia. Br J Haematol 2001;114:70-77.
33. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:1361-1392.
34. Rai KR, Cronkite EP, Sawitsky A, Chandra P, Steinberg J. Studies in chronic lymphocytic leukemia: blood lymphocyte surface characteristics and immunologic functional status of patients and correlation with clinical stage. Ann NY Acad Sci 1985;459:336-343.
35. Aiello A, Delia D, Borrello MG, Biassoni D, Giardini R, Fontanella E, et al. Flow cytometric detection of the mitochondrial BCL-2 protein in normal and neoplastic human lymphoid cells. Cytometry 1992;13:502-509.
36. Ruvolo PP, Deng X, Carr BK, May WS. A functional role for mitochondrial protein kinase C-α in Bcl-2 phosphoryhlalion and suppression of apoplosis. J Biol Chem 1998;273:25436-25442.
37. Warnke R, Levy R, Detection oF T and B cell antigens with hybridoma monoclonal antibodies. A biotin avidin horseradish peroxidase method. J Histochem Cytochem 1980;28:771-776.
38. Taube A. Sensitivity, specificity and predictive values: a graphical approach. Stat Med 1986;5:585-591.
39. Metz CE. Basic principles of ROC analysis. Semin Nucl Med 1978;8:283-298.
40. McConkey DJ, Chandra J, Wright S, Plunket W, McDonnell TJ, Reed JC, et al. Apoptosis sensitivity in chronic lymphocytic leukemia is determined by endogenous endonuclease content and relative expression of BCL-2 and BAX. J Immunol 1996;156:2624-2630.
41. Robertson LE, Plunkett W, McConnell K, Keating MJ, McDonnell TJ. Bcl-2 expression in chronic lymphocytic leukemia and its correlation with the induction of apoptosis and clinical outcome. Leukemia 1996;10:456-459.
42. Schena M, Larsson LG, Gottardi D, Gaidano G, Carlsson M, Nilsson K, et al. Growth and differentiation associated expression of bcl-2 in B-chronic lymphocytic leukemia cells. Blood 1992;79:2981-2989.
43. Hanada M, Delia D, Aiello A, Stadtmauer E, Recd JC, Bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocylic leukemia. Blood 1993;82:1820-1828.
44. + B cells the expression of Bcl-2 gene family is shified toward protection from apoptosis. Br J Haematol 1996;94:612-618.
45. Fegan C, Chronic lymphocytic leukemia: one cell, two diseases? Lancet 2002;360:184-186.
46. McDonnell TJ, Bcham A, Sarkiss M, Andersen MM, Lo P, Importancc of the Bcl-2 family in cell death regulation. Experientia 1996;52:1008-1017.
47. Aviram A, Rabizadeh E, Zimra Y, Yeshoron M, Marmelstein M, Haklai M, et al. Expression of bcl-2 and bax in cells isolaled from B-chronic lymphocytic leukemia patients al different stages of the disease. Eur J Haematol 2000;64:80-84.
48. Pepper C, Hoy T, Bentley P, Elevated Bcl-2/Bax are a consistent feature of apoptosis resistance in B-cell chronic lymphocylic leukaemia and are correlated with in vivo chemoresistance. Leuk Lymphoma 1998;28:355-361.
49. Pepper C, Thomas A, Hoy T, Bentley P. Chlorambucil resistance in B-cell chronic lymphocytic leukaemia is mediated through failed Bax induction and selection of high Bcl-2 expressing subclones. Br J Haematol 1999;104:581-588.
50. Klein A, Miera O, Bauer O, Golfier S, Schriever F. Chemosensitivity of B cell chronic lymphocytic leukemia and correlated expression of proteins regulating apoptosis, cell cycle and DNA repair. Leukemia 2000;14:40-46.
51. Thomas A, Pepper C, Hoy T, Bentley P. Bcl-2 and Bax expression and chlorambucil-induced apoptosis in the T cells and leukaemic B-cells of untreated B-cell chronic lymphocytic leukaemia patients. Leuk Res 2000;24:813-821.
52. Stoetzer OJ, Pogrebniak A, Scholz M, Pelka-Fleischer P, Gullis E, Darsow M, et al. Drug-induced apoptosis in chronic lymphocytic leukemia. Leukemia 1999;13:1873-1880.
53. Rabizadeh E, Bairey O, Aviram A, Ben-Dror I, Shaklai M, Zimra Y. Doxorubicin and a butyric acid derivative effectively reduce levels of Bcl-2 protein in the cells of chronic lymphocytic leukemia patients. Eur J Haemtol 2001;6:263-271.
54. 1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia: correlation with Bcl-2 and Bax. Leukemia 1999;13:266-274.
55. Osorio LM, De Santiago A, Aguilar-Santelises M, Mellsledt H, Jondal M. CD6 ligation modulates the Bcl-2/Bax ratio and protects chronic lymphocylic leukemia B cells from apoplosis induced by anti-IgM. Blood 1997;89:2833-2841.
56. Pepper C, Thomas A, Hoy T, Coller F, Bentley P. Antisense-mediated suppression of Bcl-2 highlights its pivotal tole in failed apoptosis in B-cell chronic lymphocytic leukaemia. Br J Haematol 1999;107:611-615.
57. Pepper C, Thomas A, Hoy T, Benlley P. Antisense oligonucleotidess complementary to Bax transcripts reduce the susceptibility of B-cell chronic lymphocylic leukemia cells to apoplosis in a bcl-2 independent manner. Br J Haematol 2002;43:2003-2009.
58. Konig A, Schwartz G, Mohammed R, Alkatib A, Gabrilove J. The novel cyclin-dependent kinase inhibitor flavopiridol down-regulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines. Blood 1997;90:4307-4312.
59. Chritodoulopoulos G, Fotouhi N, Krajewski S, Reed JC, Alaoui-Jamali M, Panasci L. Relationship between nitrogen mustard drug resistance in B-cell chronic lymphocytic leukemia (B-CLL) and protein expression of Bcl-2, Bax, Bcl-X and p53. Cancer Lett 1997;121:59-67.
60. Santini V, Gozzini A, Scappini B, Caporale R, Zoccolante A, Rigacci L, et al. Induction of apoptosis by monosaccharide butytate stable derivatives in chronic lymphocytic leukemia cells. Haematologica 1999;84:897-904.
61. Zaja F, Di Loreto C, Amoroso V, Sahnaso F, Russo D, Silvestri F, et al. BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludurabine and 2-chlorodeoxyadenosine. Leuk Lymphoma 1998;28:567-572.
62. Raghoebier S, van Krieken JH, Kluin-Nelemans JC, Gillis A, van Ommen GJ, Ginsberg AM, et al. Oncogene rearrangements in chronic B-cell leukemia. Blood 1991;77:1560-1564.
63. Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC, Perucho M, et al. Somatic frameshift mutations in the bax gene in colon cancers of the microsatellite mutator phenotype. Science 1997;275:967-969.
64. Meijerink JP, Mensink EJ, Wang K, Sedlak TW, Sloetjes AW, de Wille T, et al. Hematopoietic malignancies, demonstrate loss-of-function mutations of bax. Blood 1998;91:2991-2997
65. Saxena A, Moshynska O, Sankaran K, Viswanathan S, Sheridan DP. Association of a novel single nucleotide polymorphism, G(-248)A in the 5′-UTR of Bax gene in chronic lymphocytic leukemia with disease progression and treatment resistance. Cancer Lett 2002;187:199-205.
66. Clemens MJ, Bommer UA. Translational control: the cancer connection. Int J Biochem Cell Biol 1999;31:1-23.
67. Moshynska O, Sheridan DP, Kanthan R, Saxena A. Mcl-1 gene nucleotide replacements in B-cell chronic lymphocylic leukemia. Mod Pathol 2002;256A(abstract 1066).
68. Zha H, Aime-Sempe C, Salo T, Reed JC. Pro-apoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizcs with Bax via a novel domain (BH3) distinct from BH1 and BH2. J Biol Chem 1996;271:7440-7444.
69. Bodrug SE, Aime-Sempe C, Sato T, Krajewski S, Hanada M, Reed JC. Biochemical and functional comparisons of Mcl-1 and Bcl-2 proteins: evidence for a novel mechanism of regulating Bcl-2 family protien function. Cell Death Differ 1995;2:173-176.
70. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature 2000;407:802-809.
71. Kelekar A, Thompson CB. Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 1998;8:324-330.
72. Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad a heterodimeric partner for Bcl-XL and Bcl-2 displaces Bax and promotes cell death. Cell 1995;80:285-291.
73. Kozopas S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, et al. MCLI, a gene expressed in programmed myeloid cell diffirentiation has sequence similarity to BCL2. Proc Natl Acad Sci U S A 1993;90:3516-3520.
74. Reed JC. Bcl-2 family proteins: role in dysregulation of apoptosis and chemoresistance in cancer. In: Martin SJ. editor. Apoptosis and cancer. Basel: Karger Landes Systems: 1997. p 64-97.