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Title: [Characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia].
Author: Wang J, Zhang Y, Zu Y, Li Z, Li M, Song Y.
Journal: Zhonghua Xue Ye Xue Za Zhi; 2016 Feb; 37(2):110-4. PubMed ID: 27014979.
Abstract:
OBJECTIVE: To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML). METHODS: The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing. RESULTS: In 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months. CONCLUSION: T315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS. 目的: 分析伴T315I突变的Ph染色体阳性急性淋巴细胞白血病(Ph⁺ALL)和慢性髓性白血病(CML)的特征及疗效。方法: 收集2014年3月至2015年6月于郑州大学附属肿瘤医院行ABL激酶区突变检测并对酪氨酸激酶抑制剂(TKI)耐药的23例Ph⁺ ALL患者和95例CML患者的临床资料。采用R显带法进行染色体分析，实时定量PCR方法检测BCR-ABL融合基因，TRIzol法提取总RNA，直接测序法检测ABL激酶区突变。结果: ABL激酶区突变发生率在TKI耐药Ph⁺ ALL和CML中分别为60.9%(14/23)、41.1%(39/95)，其中T315I突变发生率分别为34.8%(8/23)和5.3%(5/95)，差异具有统计学意义(χ²=13.586，P<0.01)。CML慢性期患者ABL激酶区突变发生率为38.8%(19/49)，加速期、急变期分别为47.1%(8/17)、41.4%(12/29)，差异无统计学意义(χ²=0.360，P=0.835)。Ph⁺ ALL、CML患者自开始TKI治疗至发生T315I突变的中位时间分别为10和19个月，T315I突变发生至死亡或随访终止的中位时间分别为2和3个月，中位血液学缓解持续时间分别为10和16个月，中位总生存时间分别为13和42个月。结论: Ph⁺ ALL较CML更易出现T315I突变，但两者自开始TKI治疗至发生T315I突变的中位时间相近，在现有方案治疗下，两者血液学缓解持续时间、总生存时间相近。

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