The role of the c-fms oncogene in the regulation of HL-60 cell differentiation.

TLDR: It is concluded that HL-60 cells differentiate into macrophages along two different pathways: one is involved in the action of the c-fms oncogene and the other is not, and an autocrine circuit of M-CSF (or CSF-1) action may exist in the macrophage formation induced by PMA and hrGM- CSF.

Abstract: Human promyelocytic leukemia HL-60 cells were induced to differentiate into macrophages by PMA (phorbol 12-myristate-13-acetate), 1-alpha-25-(OH)2D3(1-alpha-25-dihydroxyvitamin D3, hrGM-CSF (human recombinant granulocyte-macrophage colony-stimulating factor) and into granulocytes by DMSO (dimethylsulfoxide). We found that the differentiation of HL-60 cells into macrophages was accompanied by transcription of the c-fms oncogene, which was assessed by a modified PCR (polymerase-chain reaction) method. After treatment with a c-fms anti-sense oligomer, the PMA and hrGM-CSF induced macrophage differentiation of HL-60 cells was significantly inhibited, whereas either 1-alpha-25-(OH)2D3 induced macrophage or DMSO and hrGM-CSF induced granulocytic differentiation was not inhibited. Furthermore, we treated the HL-60 cells with M-CSF (macrophage-colony stimulating factor or CSF-1) anti-sense N degrees 2 (see Figure 1) in the presence of PMA, hrGM-CSF, 1-alpha-25-(OH)2D3 and DMSO. The results showed that this treatment leads to a significant inhibition of PMA and hrGM-CSF-induced macrophage differentiation, but has no influence on the 1-alpha-25-(OH)2D3-induced macrophage differentiation and DMSO-induced granulocytic differentiation. It was further demonstrated that the M-CSF (or CSF-1) and c-fms antisense oligomers acted synergistically on inhibition of macrophage formation induced by PMA and hrGM-CSF, but had no inhibitory effect on the macrophage formation induced by 1-alpha-25-(OH)2D3. Thus we concluded firstly, that HL-60 cells differentiate into macrophages along two different pathways: one is involved in the action of the c-fms oncogene and the other is not. Secondly, an autocrine circuit of M-CSF (or CSF-1) action may exist in the macrophage formation induced by PMA and hrGM-CSF.