Granulocyte macrophage colony-stimulating factor enhances retinoic acid-induced gene expression

Journal of Leukocyte Biology

Lisa Esaki¹  Hiroko Mizuno¹  Takahisa Shimizu¹  Ken Takeda¹ 

[1] Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, JapanDepartment of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, JapanDepartment of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan

关键词: leukemia;    differentiation;    retinoic acid;    GM-CSF;    cDNA microarray;   

DOI  :  10.1189/jlb.0905502

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

We reported previously that treatment of human myeloblastic leukemia ML-1 cells with all-trans retinoic acid (ATRA) in combination with GM-CSF enhances the granulocytic differentiation, which is induced only slightly by ATRA alone. To investigate the mechanism underlying this differentiation and the synergistic effect of ATRA and GM-CSF, we used cDNA microarray to examine gene expression profiles of ML-1 cells treated with ATRA and/or GM-CSF. We identified 22 up-regulated genes in ML-1 cells treated with both reagents and examined the expression of these genes in cells treated with ATRA and/or GM-CSF by Northen blot analysis. Comparison of cells treated with both reagents and cells treated with ATRA or GM-CSF alone revealed that expression of nine of the 19 genes was induced synergistically by combined treatment with ATRA and GM-CSF. Expression of most of these genes was increased only slightly by ATRA alone, and this induction was enhanced by the addition of GM-CSF. These results indicate that GM-CSF enhances ATRA-induced gene expression. Moreover, studies with inhibitors of signaling molecules suggested that activation of JAK2 is associated with the synergistic induction of several genes by ATRA and GM-CSF. JAK2 inhibitor suppressed induction of NBT-reducing activity in ML-1 cells treated with both reagents. It is likely that the enhancer effect of GM-CSF on ATRA-induced gene expression leads to the differentiation induced synergistically by ATRA combined with GM-CSF. Further studies of the mechanism underlying this effect may identify better approaches for the treatment of RA-insensitive leukemia.

【 授权许可】

Unknown