ATRA and As2O3 regulate differentiation of human hematopoietic stem cells into granulocyte progenitor via alteration of HoxB8 expression

W.-J. Liu, N.-J. Jiang, Q.-L. Guo, Q. Xu

Department of Pediatrics, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China. lwjlyfy@qq.com

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• Stem Cells

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.

MATERIALS AND 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.

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