Objective: The cytochrome P450 subfamily IIIA5 (CYP3A5) gene is responsible for the metabolism of many clinically used anticancer agents. So far the studies on CYP3A5 gene has only been focused on the leukemia cell lines. This study examined the polymorphism of CYP3A5 and tried to find the possible relationship between CYP3A5 gene expression and treatment outcome or prognosis in children with acute leukemia.
Methods: The genotype distribution of CYP3A5-6986A/G gene polymorphism was detected with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 66 children with newly diagnosed acute leukemia (AL) and 22 control individuals. Quantitative real-time RT-PCR was used to examine wt-CYP3A5 and SV1-CYP3A5 mRNA levels in the bone marrow.
Results: Three genotypes of CYP3A5-6986A/G polymorphisms were found: CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3. There were significant differences in the wt-CYP3A5 mRNA expression among the AL patients with different genotypes (p<0.05). In patients with acute lymphocytic leukaemia (ALL), the complete remission (CR) rate in the group with a low expression of wt-CYP3A5 mRNA was significantly higher than that in the group with a high expression (p<0.05). A dynamic monitoring for wt-CYP3A5 mRNA expression was performed in two cases of ALL. The expression increased before ALL relapse compared with that in CR in a patient, while in the other patient, the expression was kept in a low level and the patient remained in CR CONCLUSIONS: wt-CYP3A5 mRNA expression was associated with the treatment outcome and prognosis in children with AL. Dynamic monitoring for wt-CYP3A5 mRNA expression in the bone marrow may be useful in the evaluation of the disease severity in childhood acute leukemia.