Abstract
Acute myeloid leukemia (AML), caused by abnormal proliferation and accumulation of hematopoietic progenitor cells, is one of the most common malignancies in adults. We reported here DYRK1A expression level was reduced in the bone marrow of adult AML patients, comparing to normal controls. Overexpression of DYRK1A inhibited the proliferation of AML cell lines by increasing the proportion of cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was due to downregulation of c-Myc by DYRK1A, through mediating its degradation. Moreover, overexpression of c-Myc markedly reversed AML cell growth inhibition induced by DYRK1A. DYRK1A also had significantly lower expression in relapsed/refractory AML patients, comparing to newly-diagnosed AML patients, which indicated the role of DYRK1A in chemoresistance of AML. Our study provided functional evidences for DYRK1A as a potential tumor suppressor in AML.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Cell Cycle / genetics
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Cell Line, Tumor
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Cell Proliferation
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Down-Regulation
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Drug Resistance, Neoplasm / genetics*
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Dyrk Kinases
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Female
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Gene Expression Regulation, Leukemic*
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Humans
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Leukemia, Myeloid, Acute / diagnosis
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Leukemia, Myeloid, Acute / drug therapy
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Leukemia, Myeloid, Acute / genetics*
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Leukemia, Myeloid, Acute / metabolism*
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Male
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Middle Aged
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins c-myc / genetics*
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Recurrence
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Young Adult
Substances
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Proto-Oncogene Proteins c-myc
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
Grants and funding
This work was supported by National Natural Science Foundation of China Grant 81171030 (X. Sun), 81370662 (C. Ji), and 81000223 (S. Zang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.