演題詳細

一般口演 / Oral Session

【E】一般口演 9 (Oral Session 9) :CML:Basic Research 1

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日程
2013年10月11日(金)
時間
09:30 - 10:30
会場
第7会場 / Room No.7 (ロイトン札幌 2F リージェント)
座長・司会
木村 晋也 (Shinya Kimura):1
1:Blood and Lung and Tumor Institute, Saga University, Japan
 
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Influence of ABCB1, ABCG2 and ABCC2 haplotype in mediating imatinib resistance among CML patients

演題番号 : OS-1-42

Anthony Z.L. Au:1、Ravindran Ankathil:1、Sim A Goh:2、Fadilah S.A Wahid:3、Alan Teh:4、Aziz A. Baba:5

1:Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia、2:Dept of Medicine, Hospital Pulau Pinang, Malaysia、3:Cell Therapy Centre, UKM Medical Centre (UKMMC), Universiti Kebangsaan Malaysia, Malaysia、4:Dept of Hematology, Sime Darby Medical Center Subang Jaya, Selangor, Malaysia、5:Dept of Internal Medicine and Clinical Hematology, Universiti Sains Malaysia, Malaysia

 

Imatinib mesylate (IM) has so far been the frontline treatment in chronic myeloid leukemia (CML) with excellent results. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. We aim to investigated the association of ABCB1 T1236C (rs1128503), G2677T/A(V) (rs2032582), C3435T (rs1045642), ABCG2 G34A (rs2231137), C421A (rs2231142) and ABCC2 C-24T (rs717620) polymorphisms with markers of response to IM in CML patients. Two hundred CML patients (IM resistance and good responders, n=100 each) who initially treated with a standard dose of IM for minimum duration of 18 months were enrolled in this case control study. The response criteria were based on the European LeukemiaNet recommendations. Genotyping of ABCB1, ABCG2 and ABCC2 polymorphisms were performed by multiplex, duplex and simplex PCR-RFLP respectively. Combination haplotype of CGCACT has a higher frequencies (0.34%) among IM responders compare to IM resistant patients (x2=4.006, p=0.045). Distribution of TGCCAA haplotype was associated to IM resistant with frequencies (0.126% vs 0.059%, x2=5.055, p=0.025). Furthermore, carriers of ABCB1 T1236T and G2677V had increased the probability of achieving complete molecular response and major molecular response (MMR) compared with the non-carriers (OR:2.19; 95%CI:1.07-4.48, p=0.03 and OR:3.03; 95%CI:1.28-7.18, p=0.01 respectively). Our study suggests that haplotype combination of these SNPs was correlated with IM response while SNPs in ABCB1 may be significant predictors for MMR in CML patients.

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