title: Tumor suppressor DYRK1A effects on proliferation and chemoresistance of AML cells by downregulating c-Myc.
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.
authors.affiliation: Key Lab of Otolaryngology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Shaolei
authors.initials: S
authors.lastname: Zang
authors.affiliation: Key Lab of Otolaryngology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Lab of Otolaryngology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ji
authors.affiliation: Key Lab of Otolaryngology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Xiulian
authors.initials: X
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012008:Recurrence; D055815:Young Adult; D000097603:Dyrk Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D016271:Proto-Oncogene Proteins c-myc; D000097603:Dyrk Kinases