p89c‐Myb is not required for fetal or adult hematopoiesis

Abstract

The c-myb gene encodes two proteins, termed p75 and p89. Of these, the larger isoform is transcribed from an alternatively spliced message that contains an additional exon, exon 9A. Disruption of the c-myb locus in mice results in embryonic lethality due to defective hematopoiesis and in the adult, tissue-specific inactivation of c-myb in hematopoietic tissues blocks differentiation along several lineages. The c-myb knock-out mouse models described thus far result in the disruption of both the p75 and p89 isoforms, making it impossible to assign a definitive role to p89 c-Myb in development and hematopoiesis. We have therefore generated a nullmutant mouse where exon 9A has been systemically deleted that results in the absence of only the p89-myb transcript and protein. Unlike disruption of both forms of the c-myb gene, loss of only the p89-encoding isoform does not have any deleterious effects on mammalian hematopoiesis and development.

Myb proteins: angels and demons in normal and transformed cells

“…The 9B variant is conserved throughout vertebrates, suggesting that it plays an important role. However, a targeted knockout of the 9B/p89 variant had no apparent phenotype (206), so it is possible that the variant has specialized functions or that the loss of the variant might be compensated for by other forms of c-Myb.…”

Expression of p89c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells

“…p89 c-Mybex9b accounts for 10–15% of total c-Myb protein, an amount that could be biologically relevant because small changes in the levels of c-Myb can affect lineage choice and progenitor cell frequencies in normal hematopoiesis. 47 , 48 p89 c-Mybex9b isoform-specific knockout mice have no apparent defect in the number of steady-state mature hematopoietic cells, 40 but the long-term proliferative potential, survival and differentiation of specific progenitor subsets was not investigated in detail. Although this study suggests that, in normal cells, loss of p89 c-Mybex9b expression is compensated by expression of the more abundant p75 c-Myb isoform, it is conceivable that expression of p89 c-Mybex9b is biologically more relevant in leukemic cells, which typically rely on c-Myb expression more than their normal counterparts.…”

“…The function and requirement of the p89 c-Mybex9b isoform is understood only in part: it appears to transactivate the expression of certain c-Myb targets more effectively than the predominant p75 c-Myb isoform, 39 and yet the specific knockout of p89 c-Mybex9b expression has no deleterious consequences on mammalian hematopoiesis and development, 40 suggesting that its loss is compensated by expression of p75 c-Myb .…”

Physiological and Aberrant γ-Globin Transcription During Development

“…c-Myb is the cellular homolog of v-Myb , the avian retroviral oncogene causing myelomas and lymphomas in birds ( Wolff, 1996 ). Of the two major isoforms, isoform 2 (72 kDa) is the dominant one in human erythroid cells ( Baker et al, 2010 ; Wang et al, 2018 ). In hematopoiesis, c-MYB is expressed in immature cells of all hematopoietic lineages ( Wang et al, 2018 ); in erythropoiesis, it is required for the expansion of erythroid progenitors and must be downregulated to allow differentiation ( Emambokus et al, 2003 ).…”