Altered Expression of Hoxa1 Perturbs Haematopoiesis in a Dose-Dependent Manner and Induces Myelodysplasia in Mice

Abstract

Abstract Homeobox A1 (Hoxa1) is a highly conserved transcription factor. Through pre-mRNA splicing within exon 1, wildtype Hoxa1 (WT-Hoxa1) expresses two transcript variants: a full-length Hoxa1 (Hoxa1-FL) containing a homeobox-binding domain, and a truncated homeoboxless Hoxa1 (Hoxa1-T). We have demonstrated that the two spliceforms have opposing proliferative potential, suggesting a dominant negative role exerted by Hoxa1-T. Using in silico analysis, we found that 50% of patients with myelodysplastic syndromes (MDS) have upregulated expression of HOXA1 in CD34+ cells. Delineating this further by quantitative real-time PCR, we observed that a significant propor..