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Meis1 is critical to the maintenance of human acute myeloid leukemia cells independent of MLL rearrangements

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Abstract

Although the outcome of patients with acute myeloid leukemia (AML) has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during therapy. Sustained existence of AML blasts is a fundamental determinant for the development of leukemia and resistance to therapy. Recent evidences suggest that Meis1 is tightly associated with the self-renewal capacity of normal hematopoietic stem cells. Meis1 was also found to be essential for the development of mixed lineage leukemia (MLL)-rearranged leukemia. Whether Meis1 functions independently of MLL abnormality in the context of leukemia is unclear. Herein, we identified a distinct expression pattern of Meis1 in patients with newly diagnosed AML without MLL abnormality. High levels of Meis1 expression were found in 64 of 95 (67.4%) AML patients; whereas, 31 of 95 (32.6%) patients showed dramatically lower levels of Meis1, compared with the median level of Meis1 in healthy donors. The whole cohort and subgroup analyses further demonstrated that high Meis1 expression levels were associated with a resistance to conventional chemotherapy, compared with the group with low Meis1 levels (P = 0.014 and P = 0.029, respectively). In vitro knockdown experiments highlighted a role of Meis1 in regulating maintenance and survival of human AML cells. These results implicate that Meis1 functions as an important regulator during the progression of human AML and could be a prognostic factor independent of MLL abnormality.

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Acknowledgements

This study is supported by the Key Program of National Natural Science Foundation of China (Grant No. 81230013) and Scientific Research Foundation for Returned Scholars, Ministry of Education of China.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, 11 Xizhimen South Street, Beijing, 100044, China

    Jiangying Liu, Ya-Zhen Qin, Shenmiao Yang, Yazhe Wang, Ying-Jun Chang, Ting Zhao, Qian Jiang & Xiao-Jun Huang

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  1. Jiangying Liu
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  2. Ya-Zhen Qin
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Correspondence to Xiao-Jun Huang.

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All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The study protocols have been approved by the Ethical Committee of Peking University Institute of Hematology. All patients signed the consent forms.

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The authors declare that they have no conflict of interest.

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Liu, J., Qin, YZ., Yang, S. et al. Meis1 is critical to the maintenance of human acute myeloid leukemia cells independent of MLL rearrangements. Ann Hematol 96, 567–574 (2017). https://doi.org/10.1007/s00277-016-2913-6

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  • DOI: https://doi.org/10.1007/s00277-016-2913-6

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