Neue Veröffentlichung in "Molecular Oncology"
Somatic mutations in the MLL1 histone methyltransferase are often observed in cancers. We have studied the effects of four cancer mutations in the catalytic SET domain of MLL1 which all had strong effects on the activity of MLL1. R3903H was inactive and S3865F showed reduced activity. By contrast, R3864C and R3841W were both more active than wildtype MLL1, and both mutants were not stimulated by complex formation with three other proteins, which strongly stimulates the activity of wildtype MLL1 indicating a loss of the endogenous regulation of MLL1 activity. Moreover, both mutants was not inhibited by addition of the MM-102 compound, which is a strong inhibitor of wildtype MLL1. Our data exemplify that biochemical investigations of somatic tumor mutations are required to decipher their pathological role and select an appropriate treatment.