Correlations between 6-mercaptopurine treatment-related adverse reactions in children with acute lymphoblastic leukemia and polymorphisms of thiopurine methyltransferase gene.
- Author:
Cai XIE
1
;
Li-Jie YUE
;
Hui DING
;
Yan-Fei REN
;
Chun-Lan YANG
;
Miao-Miao ZHENG
Author Information
- Publication Type:Journal Article
- MeSH: Child; Child, Preschool; Female; Humans; Male; Mercaptopurine; adverse effects; Methyltransferases; genetics; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; drug therapy; genetics
- From: Chinese Journal of Contemporary Pediatrics 2014;16(5):499-503
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore 6-mercaptopurine (6-MP) treatment-related adverse reactions in children with acute lymphoblastic leukemia (ALL), and to assess the association between the polymorphisms of thiopurine methyltransferase (TPMT) gene and these 6-MP related toxicities.
METHODSTotal RNA was extracted from bone marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE) combining with DNA sequencing. Drug toxicities were classified according to national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP treatment was analyzed.
RESULTSDuring the maintenance treatment period, 22% (10/46) of children discontinued 6-MP treatment because of serious adverse reactions. Two children with TPMT(*)3C genotypes presented severe adverse reactions, including 1 child with homozygotic mutation who had 6-MP dose-related myelosuppression and hepatotoxicity. The main side effects of 6-MP were myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no significant differences between TPMT(*)1S genotypes and severe myelosuppression or hepatotoxicity caused by 6-MP (P>0.05).
CONCLUSIONSTPMT(*)3C may correlate with severe adverse reactions caused by 6-MP.
