[Correlation between MDR1 genetic polymorphism and prognosis in acute myeloid leukemia].

OBJECTIVE

To assess the correlation of the multidrug resistance-1 (MDR1) gene single nucleotide polymorphisms (SNP) C1236T, G2677T/A and C3435T with the outcome of induction chemotherapy in patients with de novo acute myeloid leukemia (AML).

METHODS

A total of 44 AML patients were enrolled in this study. Genotype of MDR1 C1236T, G2677T/A and C3435T were analyzed with PCR/PFLP assay. Bone marrow smear was made at the end of the first induction chemotherapy to estimate whether complete remission (CR) has been achieved with the clinical characteristics. The Hardy-Weinberg equilibrium for the MDR1 C1236T, G2677T/A and C3435T were tested using a chi(2) analysis. Frequencies of genotype and allele in MDR1 C1236T, G2677T/A and C3435T were compared using a chi(2) test or Fisher's test in terms of the clinical characteristics or achievement of CR.

RESULTS

There were significant differences among ethnicities in exon 12, 21, 26, but which were not between healthy chinese volunteers and AML patients. The CR rate of the group with the number of white blood cells (WBC) < 10 x 10(9)/L were significantly higher than that of the group with WBC > 10 x 10(9)/L (chi(2) = 7.207, P = 0.007). There was no correlation between the MDR1 C1236T and C3435T and CR rate (P = 0.349, P = 0.074), but MDR1 G2677T/A genetic polymorphisms were strong associated with the probability of CR (chi(2) = 6.214, P = 0.045). In addition, the CR was lower in G/G genotype at -2677 than non G/G genotype (chi(2) = 6.142, P = 0.013), and was lower in C/T genotype at -3435 than non C/T genotype (chi(2) = 3.991, P = 0.046), even lower than T/T genotype (chi(2) = 5.134, P = 0.023).

CONCLUSION

With important prognostic significance, MDR1 genetic polymorphisms, such as G2677T/A can predict whether complete remission can be achieved after the first course of induction chemotherapy.