ASSOCIATION OF THE COMMON CYP1A1*2C VARIANT (ILE462VAL POLYMORPHISM) WITH CHRONIC MYELOID LEUKEMIA (CML) IN PATIENTS UNDERGOING IMATINIB THERAPY

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LAKKIREDDY SAMYUKTHA; AULA SANGEETHA; AVN SWAMY; KAPLEY ATYA; DIGUMARTI RAGHUNADHA RAO; JAMIL KAISER

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Journal: Cell Journal (Yakhteh) Year:2015 | Volume:17 | Issue:3 (67) Page(s): 510-519

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Title

ASSOCIATION OF THE COMMON CYP1A1*2C VARIANT (ILE462VAL POLYMORPHISM) WITH CHRONIC MYELOID LEUKEMIA (CML) IN PATIENTS UNDERGOING IMATINIB THERAPY

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Keywords

CYTOCHROME P-450 ENZYME SYSTEM

CYP1A1

POLYMORPHISM

CHRONIC MYELOID LEUKEMIA

IMATINIB

Abstract

Objective: Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association between single nucleotide POLYMORPHISMs (SNPs) inCYP1A1 and pathogenesis of CHRONIC MYELOID LEUKEMIA (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with theCYP1A1*2C [rs1048943: A>G] POLYMORPHISM in CML patients and its role in therapeutic response to IMATINIB mesylate (IM) affecting clinico-pathological parameters, in the Indian population.Materials and Methods: In this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genomic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2Cpolymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters.Results: We observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs.16%, P=0.0001), AG (57 vs.78%, P=0.0002) and GG (5 vs.6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs. AG in major (33 vs.67%) and poor (62 vs.31%) hematological responders, and AA vs. AG in major (34 vs.65%) and poor (78 vs.22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome.Conclusion: The higher frequency of AG in controls indicates that AG may play a protective role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards IMATINIB therapy, indicating that this POLYMORPHISM could serve as a good therapeutic marker in predicting response to such therapy.

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APA: Copy

LAKKIREDDY, SAMYUKTHA, AULA, SANGEETHA, AVN, SWAMY, KAPLEY, ATYA, DIGUMARTI, RAGHUNADHA RAO, & JAMIL, KAISER. (2015). ASSOCIATION OF THE COMMON CYP1A1*2C VARIANT (ILE462VAL POLYMORPHISM) WITH CHRONIC MYELOID LEUKEMIA (CML) IN PATIENTS UNDERGOING IMATINIB THERAPY. CELL JOURNAL (YAKHTEH), 17(3 (67)), 510-519. SID. https://sid.ir/paper/657801/en

Vancouver: Copy

LAKKIREDDY SAMYUKTHA, AULA SANGEETHA, AVN SWAMY, KAPLEY ATYA, DIGUMARTI RAGHUNADHA RAO, JAMIL KAISER. ASSOCIATION OF THE COMMON CYP1A1*2C VARIANT (ILE462VAL POLYMORPHISM) WITH CHRONIC MYELOID LEUKEMIA (CML) IN PATIENTS UNDERGOING IMATINIB THERAPY. CELL JOURNAL (YAKHTEH)[Internet]. 2015;17(3 (67)):510-519. Available from: https://sid.ir/paper/657801/en

IEEE: Copy

SAMYUKTHA LAKKIREDDY, SANGEETHA AULA, SWAMY AVN, ATYA KAPLEY, RAGHUNADHA RAO DIGUMARTI, and KAISER JAMIL, “ASSOCIATION OF THE COMMON CYP1A1*2C VARIANT (ILE462VAL POLYMORPHISM) WITH CHRONIC MYELOID LEUKEMIA (CML) IN PATIENTS UNDERGOING IMATINIB THERAPY,” CELL JOURNAL (YAKHTEH), vol. 17, no. 3 (67), pp. 510–519, 2015, [Online]. Available: https://sid.ir/paper/657801/en

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