medigraphic.com
ISSN 0016-3813 (Print)

2003, Number 6

<< Back Next >>

Gac Med Mex 2003; 139 (6)

Analysis of Bcr-abl Type Transcript and Its Relationship with Platelet Count in Mexican Patients with Chronic Myeloid Leukemia

Rosas-Cabral A, Martínez-Mancilla M, Ayala-Sánchez M, Vela-Ojeda J, Bahena-Reséndiz P, Vadillo-Buenfil M, Aviña-Zubieta JA, Salazar-Exaire D, Miranda-Peralta E, Marroquín A, Longoria-Revilla E

Language: Spanish
References: 54
Page: 553-559
PDF size: 240.23 Kb.


ABSTRACT

Problem. lt has been suggested that type of chimeric mRNA is associated with differences in the clinical and hematologic characteristics of chronic myeloid Leukemia (CML). However, prognostic value of type of chimeric mRNA bcr-abl (b3a2 or b2a2) is still controversial. Methods. We analysed 97 cases of Philadelphia-positive CML to determine mRNA type by reverse-polymerase chain reaction (RT-PCR) and its relationship with clinical features. Results: We detected b3a2 bcr-abl transcripts in 27 (28%) cases, b2a2 in 57 (59%) cases, and 13 (13%) with both mRNA transcripts b3a2/b2a2. These frequencies were the total reverse of other reports. Age, sex, hemoglobin and white-cell counts showed no significant difference for those with either b3a2 or b2a2 bcr-abl transcripts. However, platelet counts of b3a2 patients were significantly higher than those of b2a2 patients (743.3 vs 477.3 x 109/L;p = 0.01). In addition, in the subgroup of patients whose white-cell count at diagnosis was >100 x 109/L, those with b3a2 transcript had a significantly higher platelet count (679.1 vs. 352.2 x 109/L; p=0.00l). Conclusions: We observed reversed frequency of bcr-abl transcripts in this population, but according to other Latin American reports. In addition, our data suggested that there is different CML biological behaviour in our population and that there is a subpopulation of CML patients in whom the b3a2 is associated witli higher thrombopoietic activity.


REFERENCES

  1. Jandl JH. Chronic myelogenous leukemia. In: Blood. Textbook of hematology. Littie Brown, Co. First. ed. 1987. p. 671-713.

  2. 2. Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Scince 1960;132:1197-1200.

  3. 3. Hermans A, Heisterkamp N, Von Liddern M, Van Baal S, Meijer D, Van der Plas D, Weidemann LM, Groffen J, Bootsma A, Grosveld G. Unique fusion of BCR and C-ABL genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell 1987;51:33-44.

  4. 4. de Klein A, Geurts Van Kessel A, Grosveld G, Bartram CR, Hagemeier A, Boostma D, Spurr NK, Heisterkamp N, Groffen J, Sthephenson JR. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature 1982;300:765-767.

  5. 5. Heisterikamp N, Stam K, Groffen J, de Klein A, Grosveld G. Structural organization of the BCR gene and it's role in the Ph+ translocation. Nature 1985;315:758-761.

  6. 6. Shitvelman EB, Lifshitz B, Gale RP, Canani E. Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature 1986;315:550-554.

  7. 7. Bernards A, Rubin CM, Westbrook CA, Paskind M, Baltimore D. The first intron in the human c-abl gene is at least 200 kilobases long and is a target for translocation in chronic myelogenous leukemia. Mol Cell Biol 1987;7:3231-3236.

  8. 8. Groffen J, Bootsma A, Grosveld G. Unique fusion of BCR and c-ABL genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell 1987;51:33-44.

  9. 9. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the p210 bcr/abl gene of the Philadelphia chromosome. Science 1990;247,824-830.

  10. Hochhaus A, Lin F, Rieter A, Skladny H, Masson PJ, Van Rhee F, Shepherd PC, Allan N, Hehlmann R, Goldman JM, Cross NCP. Quantification of residual disease in chronic myelogenous leukemia patients on interferon therapy by competitive polymerase chain reaction. Blood 1996;87:5491-5550.

  11. Wetzler M, Talpaz M, Estrov Z, Kurzrock R. CML: mechanisms of disease initiation and progression. Leuk Lymph 1993;11:47-50.

  12. Shaefer-Rego K, Dudek M, Popenoe D, Arlin Z, Mears JG, Bank A, Leibowitz D. CML patients in blast crisis have breakpoints localized to a specific region of the BCR. Blood 1987;70:448-455.

  13. Birnie GD, Mills KI, Benn P. Does the site of the breakpoint on chromosome 22 influence the duration of the chronic phase in chronic myeloid leukemia. Leukemia 1989;3:545-547.

  14. Mills KI, MacKenzie ED, Birnie GD. The site of the breakpoint within the bcr is a prognostic factor in Philadelphia-positive CML patients. Blood 1988;72:1237-1241.

  15. Shtalrid M, Talpaz M, Kurzrock R, Kantarjian H, Trujillo J, Gutterman J, Yoffe G, Blick M. Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia positive chronic myelogenous leukemia. Blood 1988;72:485-490.

  16. Dreazen O, Berman M, Gale RP. Molecular abnormalities of bcr and c-abl in chronic myelogenous leukemia associated with a long, chronic phase. Blood 1988; 71:797-799.

  17. Przepiorka D. Breakpoint zone of bcr in chronic myelogenous leukemia does not correlate with disease phase or prognosis. Cancer Gen Cytogene 1988;36:117-122.

  18. Holyoake DT. Recent advances in the molecular and celular biology of chronic myeloid leukemia: lessons to be learned from the laboratory. Br J Haematol 2001;113:11-23.

  19. Morris SW, Daniel L, Ahmed CMI, Elias A, Leibowitz P. Relationship of bcr breakpoint to chronic phase duration, survival and blast crisis lineage in chronic myelogenous leukemia patients presenting in early chronic phase. Blood 1990;75:2035-2041.

  20. Tien HF, Wang CH, Chen YC, Shen MC, Wu HS, Lee FY, Chuang SM. Liu CH. Chromosome and bcr rearrangement in chronic myelogenous leukemia and their correlation with clinical states and prognosis of the disease. Br J Haematol 1990;75:469-475.

  21. Jaubert J, Martiat P, Dowding C, lfrah N, Goldman JM. The position of the M-BCR breakpoint does not predict the duration of the chronic phase or survival in chronic myeloid leukemia. Br J Haematol 1990;74:30-35.

  22. Zacearia A, Martinelli G, Buzzi M, Testoni N, Farabegoli P, Zuffa E, Zamagni MD, Russo D, Bacearani M, Ambrosetti A, Guerrasio A, Saglio, Tura S. The type of BCR/ABL junction does not predict the survival of patients with Ph positive chronic myeloid leukemia. Br J Haematol 1993;84-265-268.

  23. Milis KI, Benn P, Birnie GD. Does the breakpoint within the major breakpoint cluster region (M-bcr) influence the duration of the chronic phase in chronic myeloid leukemia? An analytical comparison of current literature. Blood 1991;78:1155-1161.

  24. Dobrovie A, Trainor KJ, Morley AA. Detection of the molecular abnormality in chronic myeloid leukemia by use of the polymerase chain reaction. Blood 1990;72;2063-2065.

  25. Deininger MW, Goldman JM, Melo JV. The molecular biolgy of chronic myeloid leukemia. Blood 2000;96:3343-3356.

  26. Rozman C, Urbano-lspizua A, Cervantes F, Rozman M, Colomer D, Féliz P, Vives-Corrons JL. Analysis of the clinical relevance of the breakpoint location within M-BCR and the type of chimeric mRNA in chronic myelogenous leukemia. Leukemia 1995;9:1104-1107.

  27. Stiepherd P, Sufflolk R, Halsey J, Allan NC. Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukemia. No correlation with clinical features, cytogenesis response, duration of chronic please, or survival. Br J Haematol 1 995;89:546-554.

  28. Cross NCP, Melo JV, Lin F, Goldman JM. An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in hematological disorders. Leukemia 1994;8:186-189.

  29. Pignoti JM, Henni T, Amselem S. Frequent detection of residual disease by use of the polymerase chain reaction in long-term survivors after bone marrow transplantation for chronic myeloid leukemia. Leukemia 1990;4:83-86.

  30. Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 1996;88:2375-2384.

  31. Williams DI, Harber J, Murphy SB, Look AT, Kalwinsky DK, Rivera C, Melvin SI, Stass S, Dahl GV. Chromosomal translocations play a unique role in influencing, prognosis in childhood acute lymphoblastic leukemia. Blood 1986;68:205-212.

  32. Chomczynski P. A reagent for the single-step simultaneous isolation of RNA, DNA, and proteins from cell and tissue samples. Biothecniques 1993;15:532-537.

  33. Eisenberg A, Silver R, Soper L, Arlin Z, Coleman M, Bernhardt B, Benn P. The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia. Leukemia 1988;2:642-646.

  34. Grossman A. Fine mapping, of chromosome 22 breakpoints within the breakpoint cluster region (bcr) implies a role for bcr exon 3 in determining disease dilation in chronic myeloid leukemia. Am J Hum Gellet 1989,45:729-738.

  35. Inokuchi K, Futaki M, Yamada T, Tanabe Y, Dan K, Shinohara T, Kuriya SH, Nomura T. The relationship between the site of breakpoints within the bcr gene and thrombopoiesis of philadelphia-positive chronic myelocytic leukemia. Leukemia Res 15;1067-1073.

  36. Arden JC. Molecular analysis in chronic granulocytic leukemia: location of breakpoints within M-BCR and relationship with presentation platelet counts. Clin Lab Haematol. 1993;15:253-258.

  37. Fioretos T. Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia. Leukemia 1993;7:1225-1231.

  38. Lee M, Kantarjian H, Deisseroth A, Freireich E, Trujillo J, Stalh S. Clinical investigation of bcr-abl splicing patterns by polimerase chain reaction in Philadelphia chromosome (Ph') positive chronic myelogenous leukemia (CML). Blood. 1990;75 (Suppl 1):294a.

  39. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Chronic myeloid leukemia. bcr/abl transcript, response to alfa-interferon and survival. Leukemia 1995;9:1648-1652.

  40. Opalka B, Wandl UB, Kloke O, Beer U, Seeber S, Niederle N. No correlation between site of breakpoint in the bcr gene and the platelet counts in Philadelphia chromosome-positive CML. Leuk Res 1992:16:937-939.

  41. Inokuchi K, Inotie T, Tojo A, Futaki M, Miyake K, Yamada T, Tanabe Y, Ohki I, Dan K, Ozawa K, Asano SH, Nomura T. A possible correlation between the type of bcr-abl hybrid messenger RNA and platelet count in Philadelphia positive chronic myelogenous leukemia. Blood 1991;78:3125-3127.

  42. Opalka B, Wandl U, Stutenkemper R, Kloke O, Seeber S, Niederle N. No correlation between the type of bcr-abl hybrid messenger RNA and platelet counts in chronic myelogenous leukemia. Blood 1992:80:1 854-1 855.

  43. Inokuchi k, Futaki M, Yamada T, Tanabe Y, Ohki I, Dan K, Nomura T, lnoue T, Tojo A, Ozawa K, Asano SH. Molecular breakpoints and platelet counts in chronic myeloid leukemia. Blood 1992,80: 556-557.

  44. Inokuchi K, Futaki M, Dan K, Nomura T. Possible correlation of b3-a2-type bcr-abl messenger RNA defined by semiquantitative RT-PCR to platelet and megakaryocytic counts in Philadelphia-positive chronic myelogenous leukemia. Intern Med 1994;33:189-192.

  45. Nakata Y. Bcr-abl MRNA expression in patients with chronic myeloproliferative disorders- absence of bcr-abl fused clone except chronic myelocytyc leukemia. Hiroshima J Med Sci. 1993;42:67-7

  46. Nakamura et al. Molecular studies of chronic myelogenous leukemia usig the polymerase chain ireaction. Cancer. 1993;68:2426-2430.

  47. Perego RA, Costantini M, Cornacchini G, Gargantini L, Biailchi C, Pungolino E, Rovida E, Morra E. The possible influences of B2A2 and B3A2 BCR/ABL protein structure on thrombopoiesis in chronic myeloid leukemia. Eur J Cancer 2000;36:1395-1401.

  48. Cervantes F, Colomer D, Vives-Corrons JL, Rozman C, Montserrat E. Chronic myeloid leukemia of thrombocytemic onset: a CML subtype with distinct hematological and molecular features? Leukemia 1996;10:1241-1243.

  49. Shitvelman EB, Gale RP, Dreazen O, Berrebi A, Zaizov R, Ktibonishi I, Miyoshi I, Canaani E. bcr-abl RNA in patients with chronic myelogenous leukemia. Blood 1987;69:971-973

  50. MacKenzie E, Stewart E, Birnie GD. ABL-BCR mRNAs transcribed from chromosome 9q+ in Philadelphia-chromosome-positive chronic myeloid leukemia. Leukemia 1993;7:702-706.

  51. Melo RAM, Melo FCBC, Lima DF, Seaffo MHS, Fernades RC, Ismael GFV, Bighetti JPM, Zago MA, Simoes BP. Lack of clinical relevance of the type of chimetric MRNA in chronic myelogenous leukemia: a study of 90 patients. Blood 1997;90:4018a.

  52. Paz-y-Mino C, Burgos R, Morillo SA, Santos JC, Fiallo BF, Lione PE. BCR/ABL rearrangement frequencies in chronic myeloid leukemia and acute lymphoblastic leukemia in Ecuador. South America. Cancer Genet Cytogenet 2002;132(1):65-67.

  53. Aurer I, Butturini A, Gafe RP. BCR-ABL rearrangements in children with Philadelphia chromosome-positive chronic myelognous leukemia. Blood 1991;78:2407-2410.

  54. Prewzer W. Relationship of the BCR gene breakpoint and the type of BCR/ABL transcript to clinical curse, prognostic indexes and survival in patients with chronic myeloid leukemia. Med Sci Monit 2002;8(5)195-197.




2020     |     www.medigraphic.com