Wang Juan, Zhang Yanli, Zu Yingling, Li Zhen, Li Mengjuan, Song Yongping
Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450008, China.
Zhonghua Xue Ye Xue Za Zhi. 2016 Feb;37(2):110-4. doi: 10.3760/cma.j.issn.0253-2727.2016.02.005.
To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).
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.
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.
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.
探讨费城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）中T315I突变的特征及临床结局。
收集2014年3月至2015年6月在郑州大学附属肿瘤医院检测到ABL激酶结构域突变的118例对酪氨酸激酶抑制剂（TKIs）耐药的Ph(+) ALL和CML患者的临床资料。分别采用R显带、实时定量聚合酶链反应（PCR）分析核型和BCR-ABL融合基因。用TRIzol试剂提取总RNA，通过直接测序检测ABL激酶结构域突变。
在23例对TKIs耐药的Ph(+) ALL和95例CML患者中，ABL激酶结构域突变率分别为60.9%（14/23）和41.1%（39/95），T315I突变率分别为34.8%和5.3%，差异有统计学意义（χ(2)=13.586，P<0.01）。慢性期/加速期/急变期CML患者的突变率分别为38.8%（19/49）、47.1%（8/17）和41.4%（12/29），差异无统计学意义（χ(2)=0.360，P=0.835）。在Ph(+) ALL和CML患者中，从开始TKIs治疗到出现T315I突变的中位时间分别为10个月和19个月，从出现T315I到死亡/截止的中位时间分别为2个月和3个月，持续血液学缓解的中位时间分别为10个月和16个月，总生存（OS）的中位时间分别为13个月和42个月。
T315I突变在Ph(+) ALL中比在CML中更容易发生，但两种疾病在从开始TKIs治疗到出现T315I的中位时间、持续血液学缓解的中位时间和OS方面相似。
