title: ATRA and As₂O₃ regulate differentiation of human hematopoietic stem cells into granulocyte progenitor via alteration of HoxB8 expression.
abstract: OBJECTIVE
  This study aimed to investigate the effect of all-trans retinoic acid (ATRA) and/or arsenic trioxide (As2O3) on homeobox B8 (HOXB8) mRNA and protein expressions during the differentiation and proliferation of hematopoietic stem cells (HSCs) to colony forming unit-granulocyte (CFU-G) in order to explore the pathogenesis of leukemia mediated by HOXB8 at mRNA and protein level.
  
  
  METHODS
  Twelve cord blood samples were collected from the fetal placenta umbilical vein and cultured in vitro. The proliferation and differentiation of cord blood HSCs into CFU-G was continuously disrupted with 10 nmol/l of ATRA and/or 10 nmol/l of As2O3. The expression of HOXB8 mRNA and protein were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western-blot, respectively.
  
  
  RESULTS
  HOXB8 mRNA/protein expression was detected in control, ATRA, As2O3 and ATRA +As2O3 groups on days 3, 7, and 12 of culture. HOXB8 mRNA/protein expression was detectable on day 3, reached its highest level on day 7 and decreased on day 12. HOXB8 mRNA/protein expression in ATRA, As2O3 and ATRA+As2O3 was upregulated compared with control group (p < 0.05).
  
  
  CONCLUSIONS
  There is a positive relationship between HOXB8 gene expression and granulocyte progenitor hematopoiesis. ATRA/As2O3 up-regulate the expression of HOXB8 mRNA/protein, and treatment of leukemia with ATRA/As2O3 may regulate HOX gene expression.
authors: Department of Pediatrics, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China. lwjlyfy@qq.com.
authors: W-J
authors: WJ
authors: Liu
authors: N-J
authors: NJ
authors: Jiang
authors: Q-L
authors: QL
authors: Guo
authors: Q
authors: Q
authors: Xu
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D042381:Granulocyte Precursor Cells / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007231:Infant, Newborn; D010087:Oxides / Q000008:administration & dosage*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D001152:Arsenicals; C490669:HOXB8 protein, human; D018398:Homeodomain Proteins; D010087:Oxides; D012333:RNA, Messenger; D014212:Tretinoin; D000077237:Arsenic Trioxide