title: Meis1 is critical to the maintenance of human acute myeloid leukemia cells independent of MLL rearrangements.
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.
authors.affiliation: 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.
authors.forename: Jiangying
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Ya-Zhen
authors.initials: YZ
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Shenmiao
authors.initials: S
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yazhe
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: 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. Huangxiaojun@bjmu.edu.cn.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D051788:Myeloid-Lymphoid Leukemia Protein
keywords: Acute myeloid leukemia; MLL rearrangement; Maintenance; Meis1; Response to chemotherapy