RBM22-depletion delays progression through all steps of cell cycle and increases ploidy in myeloid cells

RNA-Binding Motif 22 (RBM22) is a splicing factor and a transcription regulator that plays important roles in cancer. Our goal was to document further the implication of RBM22 in cell cycle progression. Using normal human haematopoietic stem and progenitor cells and myeloid cell lines (MDS-L, HL-60), we demonstrated that RBM22 depletion reduces proliferation by delaying the progression of the G1-phase, S-phase and G2/M phase. RBM22 depletion alters mitosis, generating endomitosis and alters megakaryocyte differentiation. Altogether, we propose, for the first time, RBM22 as an essential actor of the cell cycle regulation in human haematopoietic stem and progenitor cells and myeloid cells. We demonstrated that RBM22 alteration is partially responsible for the phenotype of cytopenia of myeloid cell lineages observed in myelodysplastic syndromes (MDS) with a partial deletion of chromosome 5 (MDS with del(5q)) where one allele of RBM22 is lost. We hypothesise that the impact of RBM22 on cell cycle progression could explain some phenotypic features of other cancers.