Association of CYP1A1*2C Variant (Ile464Val Polymorphism) and Some Hematological Parameters with Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML) in Erbil-Iraq.

Sumaya Basit Abdullah; Mustafa Saber Al-Attar

doi:10.21271/ZJPAS.35.3.21

Authors

Sumaya Basit Abdullah Department of Biology, College of Science ,Salahaddin University-Erbil, Kurdistan Region, Iraq
Mustafa Saber Al-Attar Department of Biology, College of Science ,Salahaddin University-Erbil, Kurdistan Region, Iraq

DOI:

https://doi.org/10.21271/ZJPAS.35.3.21

Keywords:

CYP1A1*2C; AML; CML; Cytochrome P-450 Enzyme; Polymorphism

Abstract

Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML) are life-threatening hematological neoplasms characterized by an uncontrolled proliferation of myeloid progenitors. The phase I metabolism response, which metabolizes xenobiotics and endogenous and exogenous DNA-reactive chemical compounds that may cause genotoxicity and raise the risk of AML and CML, is catalyzed by the cytochrome P450 (CYP) enzyme. The current study is aimed to identify the frequency of CYP1A1*2C polymorphism in AML, and CML patients. Also, compare some hematological parameters in AML and CML to determine the role of allele variants as a risk factor for developing leukemia. Blood samples were collected from 100 (50 AML and 50 CML) patients and 30 controls of both sexes at different age groups. Samples were analyzed for the prevalence of CYP1A1*2C polymorphism, and the results showed that Ile/Ile (AA)- Wild, Ile/Val (AG)- Hetero, and Val/Val (GG)- Homo mutant genotypes were not significantly elevated in the AML and CML group compared to the control group. However, statistically significant differences were found between the patient’s group concerning WBC and Hb estimation, and the frequency distribution of AA- genotypes in both AML and CML patients showed a significant difference. Despite the fact that individuals in the different genotypes have the same probability to develop AML and CML. During treatment genotypes for both AML and CML patients should be considered of patients with the GG genotype who have lower WBC and Hb, especially in AML which may increase disease severity.

References

BEUTLER, E., GELBART, T. & DEMINA, A. 1998a. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A, 95, 8170-4.

BEUTLER, E., GELBART, T. & DEMINA, A. 1998b. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proceedings of the National Academy of Sciences, 95, 8170-8174.

DORES, G. M., DEVESA, S. S., CURTIS, R. E., LINET, M. S. & MORTON, L. M. 2012. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood, 119, 34-43.

ESTEY, E. & DÖHNER, H. 2006. Acute myeloid leukaemia. The Lancet, 368, 1894-1907.

FERTRIN, K. Y., GONÇALVES, M. D. S., SAAD, S. T. O. & COSTA, F. F. 2002. Frequencies of UDP‐glucuronosyltransferase 1 (UGT1A1) gene promoter polymorphisms among distinct ethnic groups from Brazil. American journal of medical genetics, 108, 117-119.

GUILHOT, F., APPERLEY, J., KIM, D.-W., BULLORSKY, E. O., BACCARANI, M., ROBOZ, G. J., AMADORI, S., DE SOUZA, C. A., LIPTON, J. H. & HOCHHAUS, A. 2007. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or-intolerant chronic myeloid leukemia in accelerated phase. blood, 109, 4143-4150.

HEHLMANN, R., HOCHHAUS, A. & BACCARANI, M. 2007. Chronic myeloid leukaemia. The Lancet, 370, 342-350.

INDULSKI, J. & LUTZ, W. 2000. Metabolic genotype in relation to individual susceptibility to environmental carcinogens. International archives of occupational and environmental health, 73, 71-85.

KHWAJA, A., BJORKHOLM, M., GALE, R. E., LEVINE, R. L., JORDAN, C. T., EHNINGER, G., BLOOMFIELD, C. D., ESTEY, E., BURNETT, A. & CORNELISSEN, J. J. 2016. Acute myeloid leukaemia. Nature reviews Disease primers, 2, 1-22.

LAKKIREDDY, S., AULA, S., AVN, S., KAPLEY, A., RAO DIGUMARTI, R. & JAMIL, K. 2015. Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy. Cell J, 17, 510-9.

LU, J., ZHAO, Q., ZHAI, Y.-J., HE, H.-R., YANG, L.-H., GAO, F., ZHOU, R.-S., ZHENG, J. & MA, X.-C. 2015. Genetic polymorphisms of CYP1A1 and risk of leukemia: a meta-analysis. OncoTargets and therapy, 8, 2883.

MARCUCCI, G., HAFERLACH, T. & DÖHNER, H. 2011. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. Journal of Clinical Oncology, 29, 475-486.

OYAMA, T., KAGAWA, N., KUNUGITA, N., KITAGAWA, K., OGAWA, M., YAMAGUCHI, T., SUZUKI, R., KINAGA, T., YASHIMA, Y. & OZAKI, S. 2004. Expression of cytochrome P450 in tumor tissues and its association with cancer development. Frontiers in Bioscience-Landmark, 9, 1967-1976.

PELLOSO, L. A. F., DA SILVA, I. D. C. G., YAMAMOTO, M. & MARIA DE LOURDES, L. 2013. Increased risk of acute myeloid leukemia in patients with CYP1A1 polymorphisms.

RENDIC, S. P. & GUENGERICH, F. P. 2021. Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update. Arch Toxicol, 95, 395-472.

ROOSEBOOM, M., COMMANDEUR, J. N. & VERMEULEN, N. P. 2004. Enzyme-catalyzed activation of anticancer prodrugs. Pharmacological reviews, 56, 53-102.

ROSTAMI, G., ASSAD, D., GHADYANI, F., HAMID, M., KARAMI, A., JALAEIKHOO, H. & KALAHROODI, R. A. 2019. Influence of glutathione S‐transferases (GSTM1, GSTT1, and GSTP1) genetic polymorphisms and smoking on susceptibility risk of chronic myeloid leukemia and treatment response. Molecular Genetics & Genomic Medicine, 7, e00717.

SHIN, H. C., ROTH, H. R., GAO, M., LU, L., XU, Z., NOGUES, I., YAO, J., MOLLURA, D. & SUMMERS, R. M. 2016. Deep Convolutional Neural Networks for Computer-Aided Detection: CNN Architectures, Dataset Characteristics and Transfer Learning. IEEE Trans Med Imaging, 35, 1285-98.

SMITH, M. L., HILLS, R. K. & GRIMWADE, D. 2011. Independent prognostic variables in acute myeloid leukaemia. Blood reviews, 25, 39-51.

ZANGER, U. M. & SCHWAB, M. 2013. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther, 138, 103-41.