The two common rearrangements t(8;21) and inv(16) are found in approximately 20% of all acute myelogenous leukemias. Both aberrations result in the formation of a fusion gene, involving subunits of the core binding transcription factor (CBF). In this manuscript we hypothesize that the alternative splicing of the fusion genes, leading to truncated CBF subunits, contributes to the pathogenesis of t(8;21) and inv(16) leukemias.