POLYMORPHISM OF BIOTRANSFORMATION GENES AND RISK OF RELAPSE IN CHILDHOOD ACUTE LEUKEMIA
Gra OA1,2, Kozhekbaeva ZhM1,2,3, Makarova OV4,Samochatova EV4, Nasedkina TV1,*
*Corresponding Author: Tatyana V. Nasedkina, Ph.D., Department of Biological Microarray, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia; Tel.: +7-499-135-62-59; Fax: +7-499-135-14-05; E-mail: nased@biochip.ru, nased@eimb.ru
page: 21
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Abstract

Leukemia is a hematological malignancy that involves bone marrow. Polymorphism of biotransformation genes plays an important role in primary childhood leukemia and affects the incidence and character of acute leukemia relapse. A biochip designed to assess some polymorphisms of biotransformation genes was used to determine the frequency of the polymorphic variants of CYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19 and NAT2 in 332 children with acute lymphoblastic leukemia (ALL) and 71 children with acute myeloblastic leukemia (AML). The CYP1A1 *1/*2A, GSTT1 non null and GSTM1 non null genotypes were more frequent in patients with primary leukemia than in relapse. Analysis of the NAT2 genotype frequency revealed a characteristic genotype for each type of leukemia, whichprevailed in patients with relapse: the genotype 341C/, 481T/, 590G/G, 857G/G prevailed in ALL patients with relapse, and the genotype 341T/T, 481C/C, 590A/ in AML patients with relapse when compared with patients having primary ALL or AML, respectively. Thus, the polymorphisms of CYP1A1, GSTT1,GSTM1 and NAT2 genes can be considered as markers for risk of relapse in childhood acute leukemia and can be used for the prognosis and individualization of standard therapy.

Key words: Childhood acute leukemia; Polymorphism; Predisposition; Relapse; Microarray
 

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1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

2 Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia

3 University of Miami Miller School of Medicine Institute for Human Genomics, Miami, Florida, USA

4 Research Institute of Pediatric Hematology, Russian Federation Ministry of Health and Social Development, Moscow, Russia




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