酪氨酸激酶抑制剂治疗后慢性髓细胞白血病患者Ph阴性细胞中染色体异常的遗传学特征和转归

摘要

Objective To investigate cytogenetic features and outcome of chromosomal abnormalities in Philadelphia negative cells (Ph-CAs) of chronic myelogenous leukemia (CML) patients treated with tyrosine kinase inhibitors.Methods Clinical and laboratory data of 15 CML patients in which Ph- CAs occurred after tyrosine kinase inhibitors therapy were collected and analyzed.Results Of 15 cases with Ph-CAs,12 patients were treated with imatinib,2 were treated with dasatinib and 1 was treated with bosutinib.+8 was the most common abnormality in Ph- CAs,which accounted for 46.7％ of all.Ph CAs usually occurred when Ph+ cells decreased or disappeared due to tyrosine kinase inhibitors therapy.The average time for the appearance of Ph-CAs was 11.1 months (1-28 months).In 7 patients,the Ph-CAs have disappeared in 10.9 months (3-24 months). In such patients,no myelodysplastic syndrome or acute leukemia was observed. One patient has progressed to acute monocytic leukemia with Ph+ cells. All remaining patients have achieved bone morrow remission,among which 11 patients achieved complete cytogenic response and 4 patients even achieved complete molecular response.Conclusion The majority of Ph-CAs developed in CML patients are transient in nature.They may develop following imatinib,dasatinib or bosutinib therapy but do not interfere with the therapeutic effects of tyrosine kinase inhibitors.%目的 观察酪氨酸激酶抑制剂治疗后慢性髓细胞白血病(chronic myelogenous leukemia,CML)Ph阴性细胞中染色体异常(chromosomal abnormalities in Ph negative cells,Ph- CAs)的遗传学特征和转归.方法 对15例接受酪氨酸激酶抑制剂治疗后出现Ph- CAs的CML患者进行遗传学和分子学动态观察.结果 出现Ph- CAs患者中,依马替尼治疗12例,达沙替尼治疗2例,伯舒替尼治疗1例,染色体异常以+8最为多见,占46.7％.Ph- CAs出现在ph+克隆减少或消失时,出现的平均时间为11.1个月(1～28个月)；7例Ph- CAs已经消失,Ph- CAs持续的平均时间为10.9个月(3～24个月).Ph- CAs出现时,所有病例均未见骨髓病态造血或急性白血病；Ph- CAs出现后,除1例患者演变为ph+急性单核细胞白血病外,其余均获得骨髓缓解,11例获完全细胞遗传学反应,4例获完全分子学反应.结论 依马替尼、达沙替尼和伯舒替尼治疗CML患者均可能出现Ph- CAs；Ph- CAs多数为一过性,对酪氨酸激酶抑制剂治疗效果无影响.