A clinical observation of Chinese chronic myelogenous leukemia patients after discontinuation of tyrosine kinase inhibitors.
A clinical observation of Chinese chronic myelogenous leukemia patients after discontinuation of tyrosine kinase inhibitors.
复制标题
中国慢性粒细胞白血病患者停用酪氨酸激酶抑制剂后的临床观察
DOI：
10.18632/oncotarget.11281
复制
发表时间：
2016-09-06
期刊：
影响因子：
--
通讯作者：
Zou P
中科院分区：
文献类型：
--
作者：
Li Q;Zhong Z;Zeng C;Meng L;Li C;Luo Y;Wang H;Li W;Wang J;Cheng F;Guo A;Liu S;Jin C;Zhu X;You Y;Zou P
酪氨酸激酶抑制剂（TKI）能否安全停药是目前慢性粒细胞白血病（CML）治疗的一个关键问题。我们报告了中国CML患者停用TKI的临床观察，以及CML白血病干细胞（LSC）与复发之间的可能联系。总共有22/1057例患者同意参与本观察。TKI停药后完全分子学缓解的平均时间为12.73个月。流式细胞术检测到大部分患者的LSC。然而，LSC的数量在复发者和非复发者之间没有差异。我们通过将骨髓移植到受辐射的NOD/SCID小鼠中来评估LSC的白血病发生能力。结果表明，复发者的部分骨髓导致小鼠白血病的发生。此外，我们发现LSC衍生的微泡可能作为一个新的因素分层的不可检测的微小残留病和复发的早期预警信号。总之，TKI停药后复发似乎与LSC数量无关。小鼠异种移植模型将提供一种分析LSC功能和预测复发的新的有用方法。微泡可提供有关TKI停药策略中最佳分子监测时间表的重要信息。
Whether tyrosine kinase inhibitors (TKIs) can be safely discontinued is a key focus of chronic myelogenous leukemia (CML) at present. We report a clinical observation of TKIs cessation in Chinese CML patients and a probable connection between CML leukemia stem cells (LSCs) and relapse. In all, 22 of 1057 patients consented to participate in this observation. The average time of complete molecular response was 12.73 months after TKI withdrawal. LSCs could be flow cytometrically detected in most of the patients. However, the number of LSCs did not differ between the relapsers and non-relapsers. We evaluated the leukemogenetic ability of the LSCs by transplanting bone marrow into irradiated NOD/SCID mice. The results indicated that part of the bone marrow from the relapsers lead to leukemogensis in the mice. Besides, we found that LSCs-derived microvesicles might serve as a novel factor for the stratification of undetectable minimal residual disease and an early warning sign of relapse. In summary, post-TKI cessation relapse seems to show none association with the number of LSCs. A mouse xenograft model would provide a novel and useful method of analyzing LSCs function and predicting relapse. Microvesicles may provide important information about optimal molecular monitoring schedules in TKI discontinuation strategies.