AURORA KINASE A/MDM2-MEDIATED SETD2 LOSS OF FUNCTION IN CHRONIC MYELOID LEUKEMIA PATIENTS IN BLAST CRISIS INDUCES GENETIC INSTABILITY AND CAN BE THERAPEUTICALLY TARGETED

The SETD2 protein is a histone methyltransferase that specifically catalyzes the trimethylation of Lysine 36 on histone H3 (H3K36me3). SETD2/H3K36me3 are implicated in transcript elongation and splicing, DNA repair, chromosome segregation. SETD2 gene deletions and/or mutations (mostly frameshift or nonsense) have been reported in solid tumors (clear cell renal cell carcinoma, bladder cancer, lung cancer, melanoma, endometrial cancer) and in acute leukemias.