中文摘要：

目的 研究慢性髓性白血病（CML）患者ABL酪氨酸激酶区点突变类型与伊马替尼耐药及预后的关系.方法 收集70例伊马替尼耐药患者骨髓或外周血标本,采用巢式PCR扩增ABL激酶区,纯化后进行双向测序并与同源序列对比,结合患者临床资料进行统计学分析.结果 70例患者中32例（45.7％）检测出ABL酪氨酸激酶区点突变,慢性期、加速期及急变期突变患者分别为16、6、10例,共检测出11种突变类型,分别为T315I、E255K、C475Y、Y253H、G321W、G250E、F317L、E258K、F359V、E459K、F311I.Sokal评分中高危和Ph＋染色体伴复杂核型改变是点突变重要的危险因素,点突变与无点突变患者5年累计生存率差异无统计学意义（78.1％对84.2％,P=0.985）,但两组无事件生存率差异有统计学意义（34.4％对68.4％,P=0.034）.对于点突变患者,异基因造血干细胞移植较二代酪氨酸激酶抑制剂药物或联合化疗有更高的完全细胞遗传学反应率（P=0.001）.结论 CML ABL激酶区点突变患者较无突变患者有较差的疗效及预后,及时检测CML慢性期患者ABL激酶区点突变有助于患者治疗方案调整及改善预后,对于疾病进展期点突变患者,异基因造血干细胞移植有相对较好的疗效.

英文摘要：

Objective To analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia （CML）.Methods Nested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain.Then,the amplified product was purified and sequenced in both direction.The homologous analysis was performed in combination of clinical data.Results The ABL domain point mutations were detected in 32 patients （45.7％） including 16 patients in chronic phase （CP）,6 patients in accelerated phase （AP） and 10 patients in blast phase （BP）,which were detected as T315I,E255K,C475Y,Y253H,G321W,G250E,F317L,E258K,F359V,E459K and F311 I,respectively.Sokal score with intermediate and high risk and Ph＋ chromosome with complex karyotype were important risk factors for ABL domain point mutations.The 5-year overall survival （OS） was not significantly different between the patients with or without ABL domain point mutations （78.1％ vs 84.2％,P=0.985）,while the 5-year cumulative event-free survival （EFS） of two groups were 34.4％ and 68.4％ （P=0.034）,respectively.The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation （allo-HSCT） compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics （P=0.001）.Conclusion Patients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations.Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis.And allo-HSCT was a more effective therapy for patients with advanced phase.