[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).


CONCLUSIONS
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.
Wang
Dan
D
Department of Pharmacy, Peking University Third Hospital. Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing 100083, China.
Ke
Xiao-yan
XY
Wang
Jing
J
Xu
Fang
F
Hu
Yong-fang
YF
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012074:Remission Induction