ABCB1 유전적 다형성이 만성 골수성 백혈병 환자의 Imatinib 치료 반응에 미치는 영향: 체계적 문헌고찰 및 메타분석

• 영문명: ABCB1 Polymorphisms and Imatinib Response in Chronic Myeloid Leukemia Patients: A Systematic Review and Meta-analysis
• 발행기관: 대한약학회
• 저자명: 하혜민 천부순
• 간행물 정보: 『약학회지』제60권 제3호(2016년), 1~10쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2016.06.30

국문 초록

만성 골수성 백혈병은 조혈모세포의 이상으로 과립구 백혈구가 과도하게 증식하는 만성 골수증식성 암이다. 만성 골수성 백혈병 환자에서 발견되는 중요한 특징인 필라델피아 염색체 (Philadelphia chromosome)는 9번 염색체의 ABL 유전자와 22 번 염색체의 BCR 유전자의 상호전위에 의한 융합으로 생성된다. 이때 생성된 BCR-ABL 융합유전자에 의해 합성되는 발암단백질 P210 BCR-ABL은 강력한 티로신 키나아제(tyrosine kinase) 활성을 가지며 골수구 전구세포의 세포자멸사(apoptosis)를 억제하여 이 세포들의 비정상적인 증폭을 일으켜 결국 백혈병을 초래한다.

영문 초록

A growing number of studies have demonstrated that ABCB1 gene polymorphisms are associated with the variability of responses to imatinib. However, the effects of ABCB1 polymorphisms on imatinib response in chronic myeloid leukemia (CML) are inconsistent. The aim of the present study was to clarify the associations between ABCB1 polymorphisms and imatinib response in CML. A systematic literature review was performed. The databases of PubMed, Embase, and Cochrane Library were searched for all published studies from inception to December 2015. The ollowing terms were used with functions of ‘AND’ and ‘OR’: ‘chronic myeloid leukemia’, ‘CML’, ‘ABCB1’, ‘MDR1’, ‘polymorphism’,‘SNP’, and ‘imatinib’. Using the Review Manager 5, odds ratios (ORs) were pooled to estimate the effect of ABCB1 polymorphismson imatinib response in CML. The pooled analysis showed that ABCB1 2677 G allele was significantly associated with poor response to imatinib in African and Asian patients (GG vs TT, OR: 0.32, p<0.0001; GG+GT vs TT, OR:0.44, p=0.0005). In subgroup analyses, African patients carrying ABCB1 1236 C allele exhibited higher risk for worse response, whereas Asian patients with 1236 C allele showed better response (CC+CT vs TT, OR: 0.41, p=0.008 for African;OR: 1.65, p=0.03 for Asian). There was no association between C3435T polymorphisms and imatinib response in African, Asian, and Caucasian CML patients.

키워드

ABCB1 C1236T polymorphism, ABCB1 G2677T polymorphism, ABCB1 C3435T polymorphism, chronic myeloid leukemia, imatinib, response