The prognostic relevance of BCR-ABL1 transcript type, Sokal score and smoke as synergestic factor with complete cytogenetic response in CML patients treated with different TKI modalities

Dariush Radin, M. Hamid, M. Kargar, Mojtaba Jafarinia
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Abstract

Background : In chronic myeloid leukemia (CML), the influence of BCR-ABL1 transcript type, Sokal risk score and smoke on disease phynotype and cytogenetic response to treatment is still unknown and arguable. The objective of this study was to determine the prognostic significance of transcript types, risk score and smoking status among patients with CML treated with different tyrosine kinase inhibitor modalities. Materials and methods : Sixty CML patients were analyzed by Multiplex RT- PCR for molecular typing and banding standard protocols to follow the cytogenetic response of medications at intervals of 3 and 6 months. Results : The most common transcript type was e14a2 (n=35, 58.3%). There was a significant difference in cumulative incidence (CI) of complete cytogenetic response (CCR) between e14a2 and e13a2 groups (P=0.04). The time to achieve CCR was shorter in e14a2 transcript (P=0.01). The risk of resistance to drug was 4 fold higher in e13a2 group compared to e14a2. No difference was observed in CI of CCR between risk score groups (P>0.05). In smoker patients with e13a2 transcript, response to drug was lower (18 fold) than to non- smokers. Conclusion : and predictive tool for response based on transcript type. The smoke in patients expressing e13a2 may be induce resistance.
BCR-ABL1转录类型、Sokal评分和烟雾作为协同因子与不同TKI方式治疗的CML患者完全细胞遗传学反应的预后相关性
背景:在慢性髓性白血病(CML)中,BCR-ABL1转录类型、Sokal风险评分和吸烟对疾病表型和细胞遗传学治疗反应的影响仍是未知和有争议的。本研究的目的是确定转录类型、风险评分和吸烟状况在接受不同酪氨酸激酶抑制剂治疗的CML患者中的预后意义。材料与方法:对60例CML患者采用多重RT- PCR进行分子分型和条带标准方案分析,每隔3个月和6个月随访药物的细胞遗传学反应。结果:最常见的转录类型为e14a2 (n=35, 58.3%)。e14a2组与e13a2组完全细胞遗传学反应(CCR)的累积发生率(CI)差异有统计学意义(P=0.04)。e14a2转录本达到CCR的时间较短(P=0.01)。e13a2组耐药风险比e14a2组高4倍。风险评分组间CCR CI差异无统计学意义(P>0.05)。在e13a2转录的吸烟者中,对药物的反应比不吸烟者低(18倍)。结论:基于转录类型的反应预测工具。表达e13a2的患者的烟雾可能会引起抵抗。
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