Overexpression of an isoform of AML1 in acute leukemia and its potential role in leukemogenesis

AML1/RUNX1 is a critical transcription factor in hematopoietic cell differentiation and proliferation. From the _AML1_ gene, at least three isoforms, _AML1a_, _AML1b_ and _AML1c_, are produced through alternative splicing. AML1a interferes with the function of AML1b/1c, which are often called AML1. In the current study, we found a higher expression level of _AML1a_ in ALL patients in comparison to the controls. Additionally, AML1a represses transcription from promotor of macrophage-colony simulating factor receptor (M-CSFR) mediated by AML1b, indicating that AML1a antagonized the effect of AML1b. In order to investigate the role of _AML1a_ in hematopoiesis and leukemogenesis _in vivo_, bone marrow mononuclear cells (BMMNCs) from mice were transduced with AML1a and transplanted into lethally irradiated mice, which develop lymphoblastic leukemia after transplantation. Taken together, these results indicate that overexpression of AML1a may be an important contributing factor to leukemogenesis