[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: Volume 32, Issue 2 (summer 2022) ::
MEDICAL SCIENCES 2022, 32(2): 139-148 Back to browse issues page
The prognostic relevance of BCR-ABL1 transcript type, Sokal score and smoke as synergestic factor with complete cytogenetic response in CML patients treated with different TKI modalities
Dariush Radin1 , Mohammad Hamid 2, Mohammad Kargar3 , Mojtaba Jafarinia4
1- PhD Student, Department of biology,Marvdasht branch,Islamic azad university,Marvdasht,Iran
2- Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran , hamid143@yahoo.com
3- Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
4- Department of biology,Marvdasht branch,Islamic azad university,Marvdasht,Iran
Abstract:   (541 Views)
Background: In chronic myeloid leukemia (CML), the influence of BCR-ABL1 transcript type, Sokal risk score and smoke on disease phynotype and cytogenetic response to treatment is still unknown and arguable. The objective of this study was to determine the prognostic significance of transcript types, risk score and smoking status among patients with CML treated with different tyrosine kinase inhibitor modalities.
Materials and methods: Sixty CML patients were analyzed by Multiplex RT- PCR for molecular typing and banding standard protocols to follow the cytogenetic response of medications at intervals of 3 and 6 months.
Results: The most common transcript type was e14a2 (n=35, 58.3%). There was a significant difference in cumulative incidence (CI) of complete cytogenetic response (CCR) between e14a2 and e13a2 groups (P=0.04). The time to achieve CCR was shorter in e14a2 transcript (P=0.01). The risk of resistance to drug was 4 fold higher in e13a2 group compared to e14a2. No difference was observed in CI of CCR between risk score groups (P>0.05). In smoker patients with e13a2 transcript, response to drug was lower (18 fold) than to non- smokers.
Conclusion: The patients with e14a2 transcript may be associated with better and faster response to imatinib. Sokal risk score is not an efficient predictive tool for response based on transcript type. The smoke in patients expressing e13a2 may be induce resistance.
Keywords: BCR-ABL transcript, Chronic myeloid leukemia, Sokal risk score, Complete cytogenetic response, TKI, Smoke
Full-Text [PDF 556 kb]   (92 Downloads)    
Semi-pilot: Cohort | Subject: Oncology
Received: 2021/09/4 | Accepted: 2021/05/30 | Published: 2022/07/1
1. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature1973;243:290-293. 2. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984;36:93-9. https://doi.org/10.1016/0092-8674(84)90077-1 3. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996 ;2:561-6. https://doi.org/10.1038/nm0596-561 4.Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-7. https://doi.org/10.1056/NEJM200104053441401 5. Rostami G, Hamid M, Jalaeikhoo H. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-7. https://doi.org/10.1056/NEJM200104053441401 6.Jain P, Kantarjian H, Patel KP, Gonzalez GN, Luthra R, Shamanna RK, et al. Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors. Blood 2016;127:1269-75. https://doi.org/10.1182/blood-2015-10-674242 7.Lucas C, Wang L, Austin G, Knight K, Watmough S, Shwe K, et al. A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials. Leukemia 2008;22:1963-6. https://doi.org/10.1038/leu.2008.225 8. Shepherd P, Suffolk R, Halsey J, Allan N. Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival. Br J Haematol 1995;89:546-54. https://doi.org/10.1111/j.1365-2141.1995.tb08362.x 9. Lucas CM, Harris RJ, Giannoudis A, Davies A, Knight K, Watmough SJ, et al. Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript. Haematologica 2009;94:1362-7. https://doi.org/10.3324/haematol.2009.009134 10.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;99:1441-7. https://doi.org/10.3324/haematol.2013.096537 11.Polampalli S, Choughule A, Negi N, Shinde S, Baisane C, Amre P, et al. Analysis and comparison of clinicohematological parameters and molecular and cytogenetic response of two Bcr/Abl fusion transcripts. Genet Mol Res 2008;7:1138-49. https://doi.org/10.4238/vol7-4gmr485 12.De Lemos J, de Oliveira CM, Scerni A, Bentes AQ, Beltrão AC, Bentes I, et al. Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia. Genet Mol Res 2005;4:803-11 . 13.Sharma P, Kumar L, Mohanty S, Kochupillai V. Sharma P, Kumar L, et al. Response to Imatinib mesylate in chronic myeloid leukemia patients with variant BCR-ABL fusion transcripts. Ann Hematol 2010;89:241-7. https://doi.org/10.1007/s00277-009-0822-7 [DOI:10.1038/243290a0]
2. Vega-Ruiz A, Kantarjian H, Shan J, Wierda W, Burger J, Verstovsek S, et al. Better Molecular Response to Imatinib for Patients (pts) with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Carrying the b3a2 Transcript Compared to b2a2. Blood 2007; 110: 1939. [DOI:10.1182/blood.V110.11.1939.1939]
3. Ugai T, Matsuo K, Sawada N, Iwasaki M, Yamaji T, Shimazu T, et al. Smoking and subsequent risk of leukemia in Japan: The Japan Public Health Center-based Prospective Study. J Epidemiol 2017;27:305-310. [DOI:10.1016/j.je.2016.07.005]
4. Mohammadi F, Rostami G, Assad D, Shafiei M, Hamid M, Jalaeikhoo H. Association of SLC22A1,SLCO1B3 Drug Transporter Polymorphisms and Smoking with Disease Risk and Cytogenetic Response to Imatinib in Patients with Chronic Myeloid Leukemia. Lab Med 2021;52:584-596. [DOI:10.1093/labmed/lmab023]
5. Björk J, Albin M, Mauritzson N, Strömberg U, Johansson B, Hagmar L. Smoking and acute myeloid leukemia: associations with morphology and karyotypic patterns and evaluation of dose-response relations. Leuk Res 2001;25:865-72. [DOI:10.1016/S0145-2126(01)00048-0]
6. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 1984;63:789-99. [DOI:10.1182/blood.V63.4.789.789]
7. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809-20. [DOI:10.1182/blood-2006-02-005686]
8. Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;10:6041-51. [DOI:10.1200/JCO.2009.25.0779]
9. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013;122:872-884. [DOI:10.1182/blood-2013-05-501569]
10. Schoch C, Schnittger S, Bursch S, Gerstner D, Hochhaus A, Berger U, et al. Comparison of chromosome banding analysis, interphase-and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases. Leukemia 2002;16:53-9. [DOI:10.1038/sj.leu.2402329]
11. Yaghmaei M, Ghafari S, Ghavamzadeh A, Alimoghaddam K, Jahani M, Mousavi S, et al. Frequency of BCR-ABL fusion transcripts in Iranian patients with chronic myeloid leukemia. Arch Iran Med 2008;11:247-251.
12. Mino C,Burgos R, Morrilo SA, 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;132:65-7. [DOI:10.1016/S0165-4608(01)00515-5]
13. Osman EA, Hamad K, Elmula IM, Ibrahim ME. Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients. Genet Mol Biol 2010;33:229-31. [DOI:10.1590/S1415-47572010005000037]
14. Lee M, Kantarjian H, Talpaz M, Deisseroth A, Freireich E, Trujillo J. Association of the responsiveness to interferon therapy with the bcr/abl splicing pattern in Philadelphia chromosome positive chronic myelogenous leukemia. Blood 1992;80:210a.
15. Hai A, Kizilbash NA, Zaidi SHH, Alruwaili J, Shahzad K. Differences in structural elements of Bcr-Abl oncoprotein isoforms in Chronic Myelogenous Leukemia. Bioinformation 2014;10:108-114. [DOI:10.6026/97320630010108]
16. Nachi M, Kihel I, Entasoltane B, Brahimi M, Yafour N, Guella D, et al. Impact of the major BCR-ABL1 transcript type on clinical and biological parameters and molecular response in patients with chronic myeloid leukemia. Hematol Oncol Stem Cell Ther 2020:S1658-3876(20)30145-X. [DOI:10.1016/j.hemonc.2020.08.003]
17. de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008;26:3358-63. [DOI:10.1200/JCO.2007.15.8154]
18. 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 Paediatr Oncol 2014;35:26-30. [DOI:10.4103/0971-5851.133707]
Send email to the article author

Add your comments about this article
Your username or Email:


XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Radin D, Hamid M, Kargar M, Jafarinia M. The prognostic relevance of BCR-ABL1 transcript type, Sokal score and smoke as synergestic factor with complete cytogenetic response in CML patients treated with different TKI modalities. MEDICAL SCIENCES 2022; 32 (2) :139-148
URL: http://tmuj.iautmu.ac.ir/article-1-1938-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 32, Issue 2 (summer 2022) Back to browse issues page
فصلنامه علوم پزشکی دانشگاه آزاد اسلامی واحد پزشکی تهران Medical Science Journal of Islamic Azad Univesity - Tehran Medical Branch
Persian site map - English site map - Created in 0.05 seconds with 29 queries by YEKTAWEB 4509