title: Live kinase B1 maintains CD34+CD38-AML cell proliferation and self-renewal.
abstract: Live kinase B1 (LKB1) has been recognized as a tumor suppressor in many human cancers; however, LKB1 maintains self-renewal of hematopoietic stem cells (HSCs). The existence of leukemia stem cells (LSCs) is responsible for drug resistance and leukemia relapse. In acute myeloid leukemia (AML), CD34+CD38-fraction is the most enriched compartment for LSCs. We found that LKB1 was upregulated in CD34+CD38-AML cells. LKB1 downregulation suppressed the long-term proliferation of CD34+CD38-AML cells, induced CD34+CD38-AML cells into G2/M phase, and enhanced the sensitivity of CD34+CD38-AML cells to chemotherapy. Furthermore, LKB1 downregulation in CD34+CD38-AML cells inhibited tumor formation in NOD-SCID mice. Downregulation of LKB1 gene makes LSCs partly loose the characters as stem cells. Gene expression microarray showed that MAPK/ERK pathway was implicated in the regulation of CD34+CD38-AML cell proliferation by LKB1. Together, these findings demonstrate that LKB1 plays an important role in the maintenance of LSCs, which may be responsible for drug resistance and AML relapse.
authors.affiliation: Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, 110039, China.
authors.forename: Huihan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Shengjing Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xin
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, 110039, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Liao
authors.affiliation: Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, 110039, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, 110039, China.
authors.forename: Zhuogang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, China. zhaochenghai1@sina.com.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Zhao
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D051997:ADP-ribosyl Cyclase 1
keywords: Acute myeloid leukemia; Leukemia stem cells; Live kinase B1