Association between the BCR-ABL gene transcripts and the laboratory hematological profile
Main Article Content
Abstract
Objective: This study describes the hematological parameters associated with the BCR-ABL gene transcripts in patients with chronic myeloid leukemia (CML). Methods: We reviewed the results of 100 detectable patients for one of the BCR-ABL gene transcripts. The eligibility criteria were based on the presence of one of the leukemic transcripts (b2a2, b3a2, and b2a2/b3a2) and complete epidemiological and hematological data. The data were obtained from the LabMaster computerized system. The Kruskal-Wallis test was used to compare the medians of the quantitative variables between the transcripts of the BCR-ABL gene and the chi-square test to compare the qualitative ones, adopting the p-value with a level of significance less than or equal to 0.05. Results: Forty-five patients (45%) presented the b2a2 transcript, 24 (24%) the b3a2 transcript and 31 (31%) a b2a2/b3a2 coexpression. Individuals who expressed the b3a2 transcript had higher leukocyte counts and platelet levels, but we found no differences compared with individuals who expressed the other transcript. Conclusion: In this study, the BCR-ABL gene transcripts did not influence the hematological parameters of patients with CML.
Article Details
Authors maintain copyright and grant the HSJ the right to first publication. From 2024, the publications wiil be licensed under Attribution 4.0 International , allowing their sharing, recognizing the authorship and initial publication in this journal.
Authors are authorized to assume additional contracts separately for the non-exclusive distribution of the version of the work published in this journal (e.g., publishing in an institutional repository or as a book chapter), with acknowledgment of authorship and initial publication in this journal.
Authors are encouraged to publish and distribute their work online (e.g., in institutional repositories or on their personal page) at any point after the editorial process.
Also, the AUTHOR is informed and consents that the HSJ can incorporate his article into existing or future scientific databases and indexers, under the conditions defined by the latter at all times, which will involve, at least, the possibility that the holders of these databases can perform the following actions on the article.
References
Dorfman LE, Floriani MA, Oliveira TMRDR, Cunegatto B, Rosa RFM, Zen PRG. The role of cytogenetics and molecular biology in the diagnosis, treatment and monitoring of patients with chronic myeloid leukemia. J Bras Patol Med Lab. 2018;54(2):83-91. https://doi.org/10.5935/1676-2444.20180015 DOI: https://doi.org/10.5935/1676-2444.20180015
Neves WB, Brito AM, Vasconcelos AP, Melo FCBC, Melo RAM. Incidence and spatial distribution of Chronic Myeloid Leukemia by regions of economic development in the state of Pernambuco, Brazil. Hematol Transfus Cell Ther. 2019;41(3):212-5. https://doi.org/10.1016/j.htct.2018.08.009 DOI: https://doi.org/10.1016/j.htct.2018.08.009
Halon K, Copland M. Chronic myeloid leukemia. Medicine. 2017;45(5):287-91. https://doi.org/10.1016/j.mpmed.2017.02.004 DOI: https://doi.org/10.1016/j.mpmed.2017.02.004
Bávaro L, Martelli M, Cavo M, Soverini S. Mechanisms of disease progression and resistance to tyrosine kinase inhibitor therapy in Chronic Myeloid Leukemia: an update. Int J Mol Sci. 2019;20(24):6141. https://doi.org/10.3390/ijms20246141 DOI: https://doi.org/10.3390/ijms20246141
Bennour A, Ouahchi I, Achour B, Zaier M, Youssef YB, Khelif A, et al. Analysis of the clinico-hematological relevance of the breakpoint location within M-BCR in chronic myeloid leukemia. Med Oncol. 2012;30(1):348. https://doi.org/10.1007/s12032-012-0348-z DOI: https://doi.org/10.1007/s12032-012-0348-z
Baccarani M, Castagnetti F, Gugliotta G, Rosti G, Soverini S, Albeer A, et al. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview. Leukemia. 2019;33(5):1173-83. https://doi.org/10.1038/s41375-018-0341-4 DOI: https://doi.org/10.1038/s41375-018-0341-4
Gaspar JC, Santana LS, Souza CMF, Caseiro MM, Giuliani RRS, Souza CB. Clonagem molecular do oncogene EZH2 de leucemia mieloide crônica e perspectivas terapêuticas. Mundo Saúde. 2015;39(3):307-15. https://doi.org/10.15343/0104-7809.20153903307315 DOI: https://doi.org/10.15343/0104-7809.20153903307315
Piedimonte M, Otone T, Afonso V, Ferrari A, Conte E, Divona M, et al. A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review. BMC Cancer. 2019;19(1):50. https://doi.org/10.1186/s12885-019-5265-5 DOI: https://doi.org/10.1186/s12885-019-5265-5
Deb P, Chakrabarti P, Chakrabarty S, Aich R, Nath U, Ray SS, et al. Incidence of BCR-ABL transcript variants in patients with chronic myeloid leukemia: Their correlation with presenting features, risk scores and response to treatment with imatinib mesylate. Indian J Med Pediatr Oncol. 2014;35(1):26-30. https://doi.org/10.4103/0971-5851.133707 DOI: https://doi.org/10.4103/0971-5851.133707
Al-Achkar W, Moassas F, Youssef N, Wafa A. Correlation of p210 BCR-ABL transcript variants with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients. J BUON. 2016;21(2):444-9. PMid:27273956
Almeida-Filho TP, Maia-Filho PA, Barbosa MC, Dutra LLA, Castro MF, Duarte FB, et al. Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase? Hematol Transfus Cell Ther. 2019;41(2):114-8. https://doi.org/10.1016/j.htct.2018.10.003 DOI: https://doi.org/10.1016/j.htct.2018.10.003
Ayatollahi H, Keramati MR, Shirdel A, Kooshyar MM, Raiszadeh M, Shakeri S, et al. BCR-ABL fusion genes and laboratory findings in patients with chronic myeloid leukemia in northeast Iran. Caspian J Intern Med. 2018;9(1):66-70. https://doi.org/10.22088/cjim.9.1.65
Khorard JS, Lavallade H, Apperley JF, Milojkovic D, Reid AG, Bua M, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008;26(29):4806-13. https://doi.org/10.1200/JCO.2008.16.9953 DOI: https://doi.org/10.1200/JCO.2008.16.9953
Castagnetti F, Gugliotta G, Breccia M, Iurlo A, Levato L, Albano F, et al. The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib. Am J Hematol. 2017;92(8):797-805. https://doi.org/10.1002/ajh.24774 DOI: https://doi.org/10.1002/ajh.24774
Balatzenko G, Vundinti BR, Margarita G. Correlation between the type of bcr-abl transcripts and blood cell counts in chronic myeloid leukemia - a possible influence of mdr1 gene expression. Hematol Rep. 2011;3(1):e3. https://doi.org/10.4081/hr.2011.e3 DOI: https://doi.org/10.4081/hr.2011.e3
Verschraegen CF, Kantarjian HM, Hirsch-Ginsberg C, Lee MD, O'Brien S, Rios MS, et al. The breakpoint cluster region site in patients with Philadelphia chromosome-positive Chronic Myelogenous Leukemia. Cancer. 1995;76(6):992-7. https://doi.org/10.1002/1097-0142(19950915)76:6<992::AID-CNCR2820760612>3.0.CO;2-L DOI: https://doi.org/10.1002/1097-0142(19950915)76:6<992::AID-CNCR2820760612>3.0.CO;2-L
Lin HX, Sjaarda J, Dyck J, Stringer R, Hillis C, Harvey M, et al. Gender and BCR-ABL transcript type are correlated with molecular response to imatinib treatment in patients with chronic myeloid leukemia. Eur J Haematol. 2015;96(4):360-6. https://doi.org/10.1111/ejh.12597 DOI: https://doi.org/10.1111/ejh.12597
Sastre DA, Argarana CE, Heller VB, Gallo M, Fernandez EN, Rodrígues CM. An analysis of multiplex-PCR in the detection of BCR-ABL transcripts in hematological disorders. Genet Mol Biol. 2007;30(3):520-3. https://doi.org/10.1590/S1415-47572007000400003 DOI: https://doi.org/10.1590/S1415-47572007000400003
Paz-y-Miño C, Burgos R, Morillo AS, Santos JC, Fiallo BF, Leone PE. BCR-ABL rearrangement frequencies in chronic myeloid leukemia and acute lymphoblastic leukemia in Ecuador, South America. Cancer Genet Cytogenet. 2002;1(1):65-67. https://doi.org/10.1016/S0165-4608(01)00515-5 DOI: https://doi.org/10.1016/S0165-4608(01)00515-5
Bonilla CAA, Torres JD, Muskus CE, Gaviria GR, Sierra JC, Sanchez MS, et al. Frecuencia de los transcriptos p190 BCR-ABL y p210 BCR-ABL en una población colombiana con leucemia mieloide crónica (LMC) usando RT-PCR cualitativa. Iatreia [Internet]. 2014 [cited 2022 Aug 22];27(4):398-409. Available from: https://bit.ly/3CqbU06
Khazaal MS, Hamdan FB, Al‐Mayah QS. Association of BCR/ABL transcript variants with different blood parameters and demographic features in Iraqi chronic myeloid leukemia patients. Mol Genet Genomic Med. 2019;7(8):e809. https://doi.org/10.1002/mgg3.809 DOI: https://doi.org/10.1002/mgg3.809
Bortolheiro TC, Chiattone CS. Leucemia Mielóide Crônica: história natural e classificação. Rev Bras Hematol Hemoter. 2008;30(suppl 1):3-7. https://doi.org/10.1590/S1516-84842008000700003 DOI: https://doi.org/10.1590/S1516-84842008000700003
Sharma P, Kumar L, Mohanty S, Kochupillai V. Response to Imatinib mesylate in chronic myeloid leukemia patients with variant BCR-ABL fusion transcripts. Ann Hematol. 2009;89(3):241-7. https://doi.org/10.1007/s00277-009-0822-7 DOI: https://doi.org/10.1007/s00277-009-0822-7
Yaghmaie M, Ghaffari SH, Ghavamzadeh A, Alimoghaddam K, Jahani M, Mousavi SA, et al. Frequency of BCR-ABL Fusion Transcripts in Iranian Patients with Chronic Myeloid Leukemia. Arch Iran Med. 2008;11(3):247-251. PMId:18426313
Thakur MK, Mani ST. Estradiol regulates APP mRNA alternative splicing in the mice brain cortex. Neurosci Lett. 2005;381(1-2):154-7. https://doi.org/10.1016/j.neulet.2005.02.014 DOI: https://doi.org/10.1016/j.neulet.2005.02.014
Jain P, Kantarjian H, Patel KP, Gonzalez GN, Luthra R, Kanagal Shamanna R, et al. Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors. Blood. 2016;127(10):1269-75. https://doi.org/10.1182/blood-2015-10-674242 DOI: https://doi.org/10.1182/blood-2015-10-674242
Mondal BC, Bandyopadhyay A, Majumdar S, Mukhopadhyay A, Chandra S, Chaudhuri U, et al. Molecular profiling of chronic myeloid leukemia in eastern India. Am J Hematol. 2006;81(11):845-9. https://doi.org/10.1002/ajh.20682 DOI: https://doi.org/10.1002/ajh.20682
Arana-Trejo RM, Ruíz Sánchez E, Ignacio-Ibarra G, Báez de la Fuente E, Garces O, Gómez Morales E, et al. BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). Clin Lab Haematol. 2002;24(3):145-50. https://doi.org/10.1046/j.1365-2257.2002.00413.x DOI: https://doi.org/10.1046/j.1365-2257.2002.00413.x
Pagnano KBB, Miranda EC, Delamain MT, Duarte GO, de Paula EV, Lorand-Metze I, et al. Influence of BCR-ABL transcript type on outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib. Clin Lymphoma Myeloma Leuk. 2017;17(11):728-33. https://doi.org/10.1016/j.clml.2017.06.009 DOI: https://doi.org/10.1016/j.clml.2017.06.009
Hanfstein B, Lauseker M, Hehlmann R, Saussele S, Erben P, Dietz C, et al. Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib. Haematologica. 2014;99(9):1441-7. https://doi.org/10.3324/haematol.2013.096537 DOI: https://doi.org/10.3324/haematol.2013.096537