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Impact of ABCB1 Gene (C3435T/A2677G) Polymorphic Sequence Variations on the Outcome of Patients with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Kashmiri Population: A Case–Control Study
Indian Journal of Hematology and Blood Transfusion ( IF 0.7 ) Pub Date : 2020-05-26 , DOI: 10.1007/s12288-020-01289-6
Shahid M Baba 1 , Arshad A Pandith 2 , Zafar A Shah 1 , Sajad A Geelani 3 , Mohammad Muzaffar Mir 4 , Javid Rasool Bhat 2 , Gul Mohammad Bhat 5
Affiliation  

Inherited polymorphic sequence variations in drug transport genes like ABCB1 impact a portion of patients with hematologic malignancies that show intrinsic or acquire resistance to treatment. Keeping in view inter-individual sensitivities for such drugs, we through this case–control study tested whether ABCB1 C3435T and G2677T polymorphisms have any influence on the risk and treatment response in patients with chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Genotyping for ABCB1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism in 100 CML and 80 B-ALL patients along with 100 age and gender matched healthy controls. ABCB1 C3435T and G2677T polymorphism showed no association with CML. Genotype distribution revealed significant higher frequency of TT genotype for both SNPs in B-ALL cases and associated with increased B-ALL risk (OR 2.5, p = 0.04 for 3435TT; OR 2.4, p = 0.04 for 2677TT). There was no significant difference in genotype frequency of 3435C > T and 2677G > T among resistant and responsive groups for the two leukemia types. Kaplan–Meier survival plots revealed significantly lower event free survival in CML and B-ALL patients that were carriers of 3435TT genotype ( p < 0.05). Multivariate analysis considered 3435TT genotype as independent risk factor for imatinib resistance in CML cases (HR 6.24, p = 0.002) and increased relapse risk in B-ALL patients (HR 4.51, p = 0.03). The current study provides preliminary evidence of a significant association between variant TT genotype and increased B-ALL risk. Also, results suggest that ABCB1 3435TT genotype increases imatinib resistance in CML and influence therapeutic outcome in B-ALL.

中文翻译:

ABCB1 基因(C3435T/A2677G)多态性序列变异对克什米尔人群慢性粒细胞白血病和急性淋巴细胞白血病患者预后的影响:病例对照研究

ABCB1 等药物转运基因中的遗传多态性序列变异会影响部分血液系统恶性肿瘤患者,这些患者对治疗表现出固有的或获得性的耐药性。考虑到个体对此类药物的敏感性,我们通过本病例对照研究测试了 ABCB1 C3435T 和 G2677T 多态性是否对慢性粒细胞白血病 (CML) 和 B 急性淋巴细胞白血病患者的风险和治疗反应有任何影响。球)。ABCB1 多态性的基因分型是通过聚合酶链反应限制性片段长度多态性在 100 名 CML 和 80 名 B-ALL 患者以及 100 名年龄和性别匹配的健康对照中进行的。ABCB1 C3435T 和 G2677T 多态性显示与 CML 没有关联。基因型分布显示 B-ALL 病例中两种 SNP 的 TT 基因型频率显着更高,并且与 B-ALL 风险增加相关(OR 2.5,3435TT p = 0.04;OR 2.4,2677TT p = 0.04)。两种白血病类型的耐药组和响应组之间3435C>T和2677G>T的基因型频率没有显着差异。Kaplan-Meier 生存图显示,携带 3435TT 基因型的 CML 和 B-ALL 患者的无事件生存率显着降低(p < 0.05)。多变量分析认为 3435TT 基因型是 CML 病例伊马替尼耐药(HR 6.24,p = 0.002)和 B-ALL 患者复发风险增加(HR 4.51,p = 0.03)的独立危险因素。目前的研究提供了变异 TT 基因型与 B-ALL 风险增加之间显着关联的初步证据。还,
更新日期:2020-05-26
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