Valproic acid exerts differential effects on CXCR4 expression in leukemic cells.
We recently reported that the histone deacetylase inhibitor, valproic acid (VPA), increases CXCR4 receptor expression and function in cord blood hematopoietic stem/progenitor cells (HSPC) and the immature, highly CD34-positive AML cell lines KG-1a and KG-1. In this study, we investigated whether VPA influences CXCR4 in CD34-negative AML cell lines (promyelocytic HL-60 and monocytic THP-1), as well as both CD34-positive and CD34-negative primary AML cells. We found that VPA (i) diminishes CXCR4 expression and chemotaxis in HL-60 cells and in the CD34-negative subtypes of primary AML cells and (ii) increases CXCR4 expression and function in the highly CD34-positive subtypes of primary AML cells. Hence, we suggest that VPA exerts different effects on CXCR4 depending on cell maturation status, and this novel finding may have important implications for AML therapy.
Gul
Hilal
H
Canadian Blood Services R & D, Edmonton, Alberta, Canada; Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2R8, Canada.
Marquez-Curtis
Leah A
LA
Jahroudi
Nadia
N
Larratt
Loree M
LM
Janowska-Wieczorek
Anna
A
D018952:Antigens, CD34; D002454:Cell Differentiation; D002633:Chemotaxis / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D019718:Receptors, CXCR4 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D018952:Antigens, CD34; D019718:Receptors, CXCR4; D014635:Valproic Acid