Abstract
Background: Reciprocal translocations like t(8;21) or inv(16) in acute myeloid leukemia (AML) usually predicts a good response to chemotherapy with a high remission rate and a relatively long median survival. MDR1/Pgp, the gene product of MDR1, is recognized as an important class of proteins for regulating pharmacokinetics. Several reports showed the effects of ABCB1 (mutidrug resistance 1 gene, MDR1, PgP) genotypes such as single nucleotide polymorphisms (SNPs) on pharmacotherapy in various malignancies including AML. However, it remains to be clarified that these SNPs of ABCB1 gene play an significant role in the treatment outcome of AML patients with favorable cytogenetics especially t(8;21) or inv(16).
Aims: To determine the prevalence and the prognostic role of ABCB1 polymorphisms in de novo AML patients with t(8;21) or inv (16).
Methods: Twenty ABCB1 gene polymorphisms (SNP numbers: rs1055302, rs1002205, rs4148750, rs7779562, rs6980101, rs1922242, rs2235013, rs4728702, rs1922240, rs1922241, rs4148734, rs6950978, rs10256836, rs1202172, rs17327442, rs7802773, rs13229143, rs4148732, rs1978095, rs10264856) were evaluated by performing DNA polymerase chain reaction assays on 49 bone marrow samples obtained at initial diagnosis from the AML patients with t(8;21) or inv(16). DNA sequencing and GeneScan analysis was performed to confirm the the genotyping results. All patients received one round of intensive induction chemotherapy consisting of 3 days of idarubicin and 7 days of cytarabine.
Results: Of total 49 patients, 39 (79.6%) were AML with t(8;21) and 10(20.4%) were AML with inv(16). The median age of patients was 37 years (range, 17–69 years). There were 29 males (59.2%) and 20 females (40.8%). There was no statistically significant difference in age, gender, leukocyte count, and percentage of peripheral or bone marrow blasts in the patients according to the ABCB1 polymophisms or cytogenetic abnormalities. However, there was significant difference in complete response (CR) rate according to the zygocities of SNPs in the intron of ABCB1 gene such as rs6980101 (genotype C/C: 68.4% vs. C/T: 100%, p=0.03), rs10256836 (G/G: 91.3% vs. G/C: 50%, p=0.03), rs17327442 (T/T: 88.9% vs. T/A: :40%, p=0.01), rs4148732 (A/A: 95.8% vs. A/G: 50%, p=0.00). CR rates were not significantly influenced by cytogenetic abnormalities. There was no significant difference in relapse rate, leukemia-free survival and overall survival between homo- and heterozygote groups in these polymorphsims.
Conclusions: This study revealed an association between ABCB1 SNPs and the treatement outcomes for AML patients with t(8;21) or inv(16). Further study is needed to reach the definite conclusion on these associations. However, a stratified treatment plan in remission induction chemotherapy such as augmentation or addition of other chemotherapeutic agents may be warranted for the AML with t(8;21) or inv(16) harvoring such ABCB1 polymophrisms.
PB1757 MORPHOLOGICAL CHARACTERISTICS, CYTOGENETIC PROFILEAND TREATMENT OUTCOME OF AML1-ETO POSITIVE ACUTE MYELOID LEUKEMIA; INDIAN PERSPECTIVE.
