Collectively, these findings highlight tumor suppressor role of SMARCB1 and illustrate SWI/SNF<sup>Δ</sup> function in maintaining an oncogenic gene expression program in AML.<b>Implications:</b> Loss of SMARCB1 in AML associates with SWI/SNF<sup>Δ</sup> nucleation, which in turn promotes Rac GTPase <i>GEF</i> expression, Rac activation, migration, and survival of AML cells, highlighting SWI/SNF<sup>Δ</sup> downstream signaling as important molecular regulator in AML.<i></i>.
Here we show that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI-SNF chromatin-remodeling complex to sustain MYC transcription, rapid cell proliferation and a block in differentiation.
Taken together, our findings provide new mechanistic insights on genomic instability linked to helicase-like transcription factor deregulation, and strongly suggest a tumor suppressor function of the SWI/SNF protein in acute myeloid leukemia.
Examination of acute myelogenous leukemia and acute lymphoblastic leukemia samples revealed a high frequency of a PASG transcript containing an in-frame 75-nucleotide deletion, which codes for a conserved motif known to be critical for the transactivation activity of a related yeast SWI/SNF polypeptide.