Impact of the Multidrug resistance 1 gene polymorphisms on the outcome of therapy in childhood acute leukemia in Duhok province/Iraq

Abstract

BACKGROUND: The multidrug resistance (MDR1) gene's polymorphism affects the metabolism and pharmacokinetics of chemotherapeutic agents and smooth drug resistance formation in malignancies and the current study aimed to evaluate the probable impact of MDR-1 gene polymorphisms (C3435T, G2677A/T) on the clinical outcome of childhood acute lymphoblastic leukemia (ALL) in Duhok/Iraq. MATERIALS AND METHODS: All enrolled patients were assessed for MDR-1 (C3435T, G2677A/T) single-nucleotide polymorphisms by means of a polymerase chain reaction followed by enzyme digestion (RFLP-PCR) assay. Response to chemotherapy was assessed by flow cytometry. RESULTS: Sixty-two patients with ALL enrolled in the current study, with a median age of 7.0 years. The main clinical features at presentations were nonspecific in the form of fatigue and loss of energy. Majority of leukemia were of B-cell origin 88.71%. Majority of patients had low hemoglobin, low platelets, and high white blood cell count mainly of blasts at presentation. Sixty-one percent of patients achieved negative minimal residual disease (MRD) after 1–2 courses of chemotherapy. The alleles frequencies at position of 2677 nucleotide were G: 24/124 (19.35%); A: 52/124 (41.94%); T: 48/124 (38.71%); and for the C3435T, frequency of C and T alleles was 54.84%, 45.16%, respectively. Achievement of negative MRD following 1–2 courses of induction, appeared significantly correlated with the age of patients at presentation. All other parameters including, sex, hematological parameters at presentation; studied polymorphism in the MDR-1 gene; and subtype of ALL were not associated significantly with MRD achievement. CONCLUSION: Polymorphic variation in MDR-1 gene, in comparison to solid tumors and chronic hematopoietic malignancies, does not have an impact on MRD achievement in ALL.