Transcriptional Repression Of Rassf2 Impairs Hippo Kinase-Dependent P53 Activation And Tumor Suppression In T(8;21) Aml

The t(8;21) chromosomal translocation is a recurring cytogenetic abnormality in acute myeloid leukemia (AML), found in ~10% of AML patients. This translocation results in the stable fusion of the RUNX1 (AML1) and RUNX1T1 genes, and formation of the oncofusion protein RUNX1-ETO (RE). One function of RE in promoting leukemia development is the recruitment of aberrant transcription factor complexes to regulatory regions of RUNX1 target genes known to be critical for myeloid differentiation, such as CEBPA, SPI1, NFE2, and CSF1R . Despite this knowledge, additional RE target genes remain poorly characterized, and the complete molecular mechanism through which RE leads to leukemic transformation remains to be elucidated.