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 this study, we found a higher expression level of AML1a in acute lymphoblastic leukemia and acute myeloid leukemia (AML)-M2 patients in comparison to the controls. Additionally, AML1a represses transcription of promoter of macrophage colony-stimulating factor receptor mediated by AML1b, indicating that AML1a antagonized the effect of AML1b. To investigate the role of AML1a in hematopoiesis and leukemogenesis in vivo , murine bone marrow mononuclear cells were transduced with AML1a and then transplanted into lethally irradiated mice, which developed lymphoblastic leukemia after transplantation. Taken together, these results indicate that overexpression of AML1a may be an important contributing factor to leukemogenesis.