Rbm5 is required for sustaining leukemia stem cells by modulating a leukemic transcriptional program in concert with the Myc network [ChIP-Seq]

Compared to other hematological malignancies, AML often predicts poor prognosis and unfavorable treatment outcomes in the clinic, urging the need for complex mechanism studies. Rbm5 was recently reported as a key regulator in maintaining the survival of human AML cell lines via non-canonical transcriptional activation of Hoxa9.

However, its function in LSCs and the broad genome-wide transcriptional targets remain elusive. Here, using genetic mouse models, ex vivo AML culture, and patient-derived xenografts, we report that Rbm5 is required for murine leukemogenesis and maintains self-renewal of LSCs in vivo but is dispensable for normal hematopoiesis. Rbm5 is highly expressed in LSCs, and its deficiency results in specifically defective LSC function, along with the inhibition of self-renewal gene expression and the induction of a myeloid differentiation program.