title: Amplified HMGA2 promotes cell growth by regulating Akt pathway in AML.
abstract: OBJECTIVE
  The aim of this study was to investigate how the amplification of HMGA2 contributes to acute myeloid leukemia (AML) cell proliferation.
  
  
  METHODS
  The amplification and expression of HMGA2 were examined by FISH, qRT-PCR and Western blot in AML cases. The effect of HMGA2 knockdown on cell proliferation was analyzed with XTT, colony-forming assays and BrdUrd incorporation assays. The effects of HMGA2 knockdown on cell cycle were studied by flow cytometry analysis. The progression of AML cells in vivo was examined by the xenografted tumor model. The interaction between Akt pathway and HMGA2 was examined by Western blot.
  
  
  RESULTS
  HMGA2 is amplified in AML, and the levels of HMGA2 messenger RNA (mRNA) and protein expressed in AML cells were significantly higher than those in normal cells, which may be related to NR and prognosis of AML patients. Reduction in HMGA2 expression in AML cells inhibited cell proliferation through a decrease in the protein expression of pAkt and pmTOR, compared with control cells.
  
  
  CONCLUSIONS
  HMGA2 is predominantly amplified and expressed in AML cells, and that aberrant expression of HMGA2 induces AML cell proliferation through the PI3K/Akt/mTOR signaling pathway. Inhibition of HMGA2 expression represents an attractive target for AML therapy.
authors: Center of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China. tanya_tanli@163.com.|Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou, 510230, China. tanya_tanli@163.com.
authors: Li
authors: L
authors: Tan
authors: Clinical Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors: Xiaoping
authors: X
authors: Wei
authors: Center of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
authors: Lixia
authors: L
authors: Zheng
authors: Center of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
authors: Jincai
authors: J
authors: Zeng
authors: Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors: Haibo
authors: H
authors: Liu
authors: Center of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
authors: Shaojiang
authors: S
authors: Yang
authors: Center of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
authors: Huo
authors: H
authors: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D005784:Gene Amplification; D055785:Gene Knockdown Techniques; D018922:HL-60 Cells; D025743:HMGA2 Protein / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D055815:Young Adult
chemical_list: D025743:HMGA2 Protein; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: AML; Akt pathway; HMGA2; Proliferation