Oncotarget

Research Papers:

A clinical observation of Chinese chronic myelogenous leukemia patients after discontinuation of tyrosine kinase inhibitors

Qing Li, Zhaodong Zhong, Chen Zeng, Li Meng, Chunrui Li, Yi Luo, Hongxiang Wang, Weiming Li, Jue Wang, Fanjun Cheng, Anyuan Guo, Songya Liu, Caibao Jin, Xiaojian Zhu, Yong You _ and Ping Zou

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Oncotarget. 2016; 7:58234-58243. https://doi.org/10.18632/oncotarget.11281

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Abstract

Qing Li1,*, Zhaodong Zhong1,*, Chen Zeng1, Li Meng2, Chunrui Li2, Yi Luo2, Hongxiang Wang3, Weiming Li1, Jue Wang2, Fanjun Cheng1, Anyuan Guo4, Songya Liu2, Caibao Jin2, Xiaojian Zhu2, Yong You1, Ping Zou1

1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China

2Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China

3Department of Hematology, the Central Hospital of Wuhan, Wuhan 430016, P. R. China

4Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

*These authors contributed equally to this work

Correspondence to:

Fanjun Cheng, email: [email protected]

Xiaojian Zhu, email: [email protected]

Yong You, email: [email protected]

Keywords: discontinuation, leukemia stem cell (LSC), monitoring, microvesicle (MV), chronic myelogenous leukemia (CML)

Received: November 03, 2015     Accepted: August 08, 2016     Published: August 13, 2016

ABSTRACT

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.


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