Fig. 7. Graphical abstract: Dual role of the epigenetic factor PSIP1 in T-ALL.

Loss-of-function mutations in patients with T-ALL in combination with an accelerated leukemic onset in two conditional Psip1 KO mouse models indicate a tumor-suppressive role for PSIP1 role in the onset of T-ALL. In addition, we propose safeguarding proper H3K27me3 occupancy as a mechanism of action for PSIP1 its tumor-suppressive function. During leukemia maintenance, we established that down-regulation of PSIP1 has a negative effect on T-ALL proliferation which is independent of KMT2A mutational status and T-ALL subtype. Furthermore, we were able to functionally link the observed phenotype to a reduced mitochondrial respiration orchestrated by down-regulation of COX20. ****P < 0.0001.