RBM5 is essential for the maintenance of leukemia stem cells by regulating a leukemic transcription program in cooperation with MYC [scRNA-seq]

RBM5 was recently reported as a key regulator in maintaining the survival of human leukemia cells via non-canonical transcriptional activation of HOXA9. However, its function in LSCs and the broad genome-wide transcriptional targets remain elusive.

Here, we report that RBM5 is required for murine leukemogenesis and maintains self-renewal of LSCs in vivo, but dispensable for normal hematopoiesis. RBM5 is highly expressed in LSCs, and its deficiency results in specifically defective LSC function with the inhibition of self-renewal gene expression and induction of myeloid differentiation program. Gene expression, chromatin accessibility, and direct genome-wide RBM5 binding further identify the direct transcriptional targets of RBM5 in primary leukemia cells including several stemness genes Hoxa9 and Myc.