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High expression of bcl-2 is the rule in acute lymphoblastic leukemia, except in Burkitt subtype at presentation, and is not correlated with the prognosis

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Gala, Jean-Luc [UCL] Vermylen, Christiane [UCL] Cornu, Guy [UCL] Ferrant, Augustin [UCL] Michaux, Jean-Louis [UCL] Philippe, Marianne [UCL] Martiat, P.

Bcl-2 expression and its prognostic value were evaluated using the APAAP technique in 40 ALL patients. Because of a possible synergy between c-myc and bcl-2 proteins in cell lines, we compared 40 ALL of either T or B lineage with seven Burkitt's ALL or sporadic Burkitt's lymphomas (BL). We found the same high expression of bcl-2 in adult (Ad) and childhood (Ch) malignancies examined at presentation, regardless of the T or B phenotype. No bcl-2 expression was detectable in BL cases, except for two investigated at relapse. Bcl-2 staining intensity was also not related to the stage of blast differentiation, except in Ad T-ALL, or to the relapse rate. Ki-67, a marker of proliferation, was used to investigate the possible correlation between bcl-2 expression and the proliferative activity. An inverse correlation was found only in BL at presentation. We confirm that bcl-2 expression is the rule in ALL, regardless of the immunophenotypic characteristics at presentation, and that high expression is not correlated with a bad prognosis. Sporadic BL may represent a particular type of tumor, with bcl-2 expression in relapse, but not at presentation.

  1. Aiello A, Delia D, Borrello MG, Biassoni D, Giardini R, Fontanella E, Pezella F, Pulford K, Pierotti M, Della Porta G (1992) Flow cytometric detection of the mitochondrial bcl-2 protein in normal and neoplastic human lymphoid cells. Cytometry 13:502–509
  2. Åkerman M, Brandt L, Johnson A, Olsson H, Mitotic activity in non-Hodgkin's lymphoma. Relation to the Kiel classification and to prognosis, 10.1038/bjc.1987.41
  3. Alnemri ES, Robertson NM, Fernandes TF, Croce CM, Litwack G (1992) Overexpressed full-length human bcl-2 extends the survival of baculovirus-infected SF9 insect cells. Proc Natl Acad Sci USA 89:7295–7199
  4. Armitage James O., Tumor Proliferative Rate and Response to Chemotherapy, 10.7326/0003-4819-116-9-771
  5. Barry MA, Behnke CA, Eastman A (1990) Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem Pharmacol 40:2353–2362
  6. Lithotripsy, 10.7326/0003-4819-103-4-626
  7. Bissonette RP, Echeveri F, Mahoubi A, Green DR (1992) Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359:552–554
  8. Browman GP, Neame PB, Soamboonsrup P (1986) The contributions of cytochemistry and immunophenotyping to the reproductibility of the FAB classification in acute leukemia. Blood 68:900–905
  9. Campana D, Coustan-Smith E, Manabe A, Buschle M, Raimondi SC, Behm FG, Ashmun R, Arico M, Biondi A, Pui CH (1993) Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2. Blood 4:1025–1031
  10. Campos L, Rouault JP, Sabido O, Oriol P, Roubi N, Vasselon C, Archimbaud E, Magaud JP, Guyotat D (1993) High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood 11:3091–3096
  11. Carson DA, Ribeiro JM (1993) Apoptosis and disease. Lancet 341:1251–1254
  12. Chen-Levy Z, Nourse J, Cleary M L, The bcl-2 candidate proto-oncogene product is a 24-kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14;18) translocation., 10.1128/mcb.9.2.701
  13. Cleary ML, Smith SD, Sklar J (1986) Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47:19–28
  14. Delia D, Aiello A, Soligo D, Fontanella E, Melani C, Pezella F, Pierotti MA, Della Porta GD (1992) bcl-2 Proto-oncogene expression in normal and neoplastic human myeloid cells. Blood 5:1291–1298
  15. Durie BGM, Mason DY, Giles F, Vela EE, Knight I, Wolff S, Foadj M, Samson D (1990) Expression of the bcl-2 oncogene protein in multiple myeloma. Blood 10 [Suppl 1]: abstract 1378
  16. Erber WN, Mynheer LC, Mason DY (1986) APAAP labelling of blood and bone marrow samples for phenotyping leukemia. Lancet 1:761–765
  17. Fiere D, Broustet A, Leblond V, Maraninchi D, Castaigne S, Flesch M, Varet B, Vernant JP, Milpied N, Troussard X (1990) Comparison of chemotherapy and autologous and allogeneic transplantation as postinduction regimen in adult acute lymphoblastic leukemia: a preliminary multicentric study. Haematol Bluttransfus 33:409–412
  18. Finke J, Fritzen R, Ternes P, Trivedi P, Bross KJ, Lange W, Mertelsmann R, Dölken G (1992) Expression of bcl-2 in Burkitt's lymphoma cell lines: induction by latent Epstein-Barr virus genes. Blood 2:459–469
  19. Gauwerky CE, Haluska FG, Tsujimoto Y, Nowell PC, Croce CM (1988) Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL-2 gene. Proc Natl Acad Sci USA 85:8548–8552
  20. Goodyear M, Soamboonsrup P, Browman G, Neame PB (1989). The contribution of cytochemistry to the classification of acute leukemia. In: Scott CS (ed) Leukemia cytochemistry and diagnosis: principles and practice. pp 201–258
  21. Graninger WB, Seto M, Boutain B, Goldman P, Korsmeyer SJ (1987) Expression of bcl-2 and bcl-2/Ig fusion transcripts in normal and neoplastic cells. J Clin Invest 80:1512–1515
  22. Grogan TM, Lippman SM, Spier CM, Slymen DJ, Rybski JA, Rangel CS, Richter LC, Miller TP (1988) Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67. Blood 4:1157–1160
  23. Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A (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
  24. Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ (1991) Bcl-2 protein topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci USA 88:6961–6965
  25. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336
  26. Kondo E, Nakamura S, Onoue H, Matsuo Y, Yoshino T, Aoki H, Hayashi K, Takahashi K, Minowada J, Nomura S, Akagi T (1992) Detection of bcl-2 protein and bcl-2 messenger RNA in normal and neoplastic lymphoid tissues by immunohistochemistry and in situ hybridization. Blood 8:2044–2051
  27. Levine EG, Arthur DC, Frizzera G, Peterson BA, Hurd DD, Bloomfield CD (1985) There are differences in cytogenetic abnormalities among histologic subtypes of the non-Hodgkin's lymphoma. Blood 66:1414–1422
  28. Liu YJ, Mason DY, Johnson GD, Abbot S, Gregory CD, Hardie DL, Gordon J, MacLennan CM (1991) Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol 21:1905–1910
  29. Lotem J, Sachs L (1993) Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and -defective myeloid leukemic cells. Cell Growth Differ 1:41–47
  30. Magrath I (1992) Molecular basis of lymphoma genesis. Cancer Res 19 [Suppl]:5529–5540
  31. McDonnel TJ, Korsmeyer SJ (1991) Progression from lymphoid hyperplasia to high grade lymphoma in mice transgenic for the t(14;18). Nature 349:254–256
  32. McDonnell TJ, Deanne N, Platt FM, Nunez G, Jaeger U, McKearn JP, Korsmeyer SJ (1989) Bcl-2-immunoglobulin transgenic mice demonstrate extended B-cell survival and follicular lymphoproliferation. Cell 57:79–88
  33. Miller Denis R., Leikin Sanford, Albo Vincent, Sather Harland, Hammond Denman, Prognostic Importance of Morphology (FAB Classification) in Childhood Acute Lymphoblastic Leukaemia (ALL), 10.1111/j.1365-2141.1981.tb02705.x
  34. Milner AE, Johnson GD and Gregory CD (1992) Prevention of programmed cell death in Burkitt lymphoma cell lines by bcl-2-dependent and -independent mechanisms. Int J Cancer 52:636–644
  35. Miyashita T, Reed JC (1993) Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 1:151–157
  36. Ngan B, Chen-Levy Z, Weiss LM, Warnke RA, Cleary ML (1988) Expression in non-Hodgkin's lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med 318:1638–1644
  37. Pezella F, Tse AGD, Cordell JL, Pulfrod KAF, Gatter KC, Mason DY (1990) Expression of bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. Am J Pathol 137:225–232
  38. Reed JC, Tanaka S, Cuddy M (1992) Cell cycle analysis of p26-BCL-2 protein levels in proliferating lymphoma and leukemia cell lines. Cancer Res 52:2802–2805
  39. Reed JC, Cuddy M, Haldar S, Corce C, Nowell P, Makover D, Bradley K (1990) BCL-2 mediated tumorigenicity of a human T-lymphoid cell line: synergy with MYC and inhibition by BCL2 antisense. Proc Natl Acad Sci USA 87:3660–3664
  40. Rosenberg SA and members of the non-Hodgkin's lymphoma pathologic classification project (1982) National Cancer Institute-sponsored study of classifications of non-Hodgkin's lymphomas. Cancer 49:2112–2135
  41. Schaison G, Sommelet D, Bancillon A, Perel Y, Leblanc T, Bergeron C, Lejars O, Baruchel A, Lepage E, Leverger G (1992) Treatment of acute lymphoblastic leukemia: French protocol Fralle 83–87. Leukemia [Suppl 2], 6;148
  42. Schena M, Larsson LG, Gottardi D, Gaidano G, Carlsson M, Nilsson K, Caligaris-Cappio F (1992) Growth- and differentiation-associated expression of bcl-2 in B-chronic lymphocytic leukemia cells. Blood 11:2981–2989
  43. Strasser A, Harris AW, Bath ML, Cory S (1990) Novel primitive lymphoid tumors induced in transgenic mice by cooperation between myc and bcl-2. Nature 348:331–333
  44. Tsujimoto Y, Cossman J, Jaffe E, Croce C (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440–1443
  45. Van Eys J, Pullen J, Head D, Boyett J, Crist W, Faletta J, Humphrey GB, Jackson J, Riccardi V, Brock (1986) The French-American-British (FAB) classification of leukaemia. Cancer 57:1046–1051
  46. Vaux DL, Cory S, Adams JM (1988) Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalise pre-B cells. Nature 335:440–442
  47. Walker PR, Smith C, Youdale T, Leblanc J, Whitfield JF, Sikorska M (1991) Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes. Cancer Res 4:1078–1085
  48. Yunis JJ, Frizzera G, Oken MM, McKenna J, Theologides J, Arnesen M (1987) Multiple recurrent genomic defects in follicular lymphoma: a possible model for cancer. N Engl J Med 316:79–84
  49. Zutter M, Hockenbery D, Silverman GA, Korsmeyer SJ (1991) Immunolocalization of the bcl-2 protein within hematopoietic neoplasms. Blood 78:1062–1068
Bibliographic reference Gala, Jean-Luc ; Vermylen, Christiane ; Cornu, Guy ; Ferrant, Augustin ; Michaux, Jean-Louis ; et. al. High expression of bcl-2 is the rule in acute lymphoblastic leukemia, except in Burkitt subtype at presentation, and is not correlated with the prognosis. In: Annals of Hematology, Vol. 69, no. 1, p. 17-24 (1994)
Permanent URL http://hdl.handle.net/2078.1/27195