Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia

Abstract

It is widely thought that c-onc genes (or proto-oncogenes)--the cellular progenitors of retroviral transforming genes--are involved in cellular differentiation and/or proliferation. Such ideas originate primarily from the ability of v-onc genes and 'activated' c-onc genes to induce uncontrolled cellular proliferation, and their capacity to arrest or interfere with differentiation processes in some systems. Haematopoietic cell populations provide additional support for these ideas as c-myb RNA is present in cell lines corresponding to immature, but not mature, cell types, and elevated levels have been found in tissues that are active in haematopoiesis. We have now examined the effects of induced differentiation on c-onc gene expression in a murine myeloid leukaemia cell line, WEHI-3B ('D+' subline). Our results show that the expression of c-myb and c-myc, at the level of transcription, decreases only at late stages in the monocytic differentiation of WEHI-3B cells, while expression of c-fos increases markedly. We suggest that c-myb and c-myc do not themselves control myeloid differentiation, but that they function in the maintenance of the proliferative state of myeloid cells. The induction of c-fos may reflect its role in some macrophage-specific functions.

The carbonic anhydrase I locus contains a c-Myb target promoter and modulates differentiation of murine erythroleukemia cells

“…c-Myb is downregulated during HMBA induced differentiation and forced expression of c-Myb can block differentiation (Gonda and Metcalf, 1984;Marks et al, 1987;Clarke et al, 1988;McClinton et al, 1990). To develop a model that would allow the identification of Myb target genes, we have generated stable transfectants in the C19 MEL cell line that carry a dominant interfering Myb transgene (MEnT).…”

Down-regulation of MLL-AF9, MLL and MYC expression is not obligatory for monocyte-macrophage maturation in AML-M5 cell lines carrying t(9;11)(p22;q23)

“…Moreover, MLL-AF9-targeted down-regulation reduces THP-1 cell growth (4,17) without affecting terminal differentiation (4). MLL oncoproteins (including MLL-AF9) can deregulate MYC transactivation activity (10), and expression of MYC maintains myeloid proliferation without, per se, controlling myeloid differentiation (18,19). Moreover, in the leukaemic K-562 cell line treated with PMA, MYC expression is down-regulated, but its ectopic overexpression does not inhibit monocyte-macrophage differentiation (20).…”

Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes.

“…A homozygous null mutation of this gene in transgenic mice resulted in the loss of hematopoietic precursors and embryonic lethality (22). The expression of c-myb decreases during differentiation (23,24) and exogenous expression of myb blocks the differentiation of hematopoietic cell lines (25)(26)(27). Only a few actual targets of c-myb are known, including mira-1 (28), a promyeloidspecific gene of unknown function, and the enhancers for the CD4 gene, the cdc2 gene, and the T cell receptor/$ chain (29)(30)(31).…”