Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia
Heather C. Murray, Anoop Enjeti, Richard G. S. Kahl, Hayley Flanagan, Jonathan R. Sillar, David A. Skerrett‐Byrne, Juhura G. Al Mazi, Gough G. Au, Charles E. de Bock, Kathryn Evans, Nathan D. Smith, Amanda L. Anderson, Brett Nixon, Richard B. Lock, Martin R. Larsen, Nicole M. Verrills, Matthew D. Dun
Abstract
Acute myeloid leukaemia (AML) is the most common and aggressive form of acute leukaemia in adults. The most common driver mutations in AML are activating mutations in the FMS-like tyrosine kinase 3 (FLT3) gene, occurring in approximately one third of cases Internal tandem duplication (FLT3-ITD) mutations in the FLT3 juxtamembrane domain are the most common (~25%), and are associated with genomic instability, and intermediateadverse prognosis Point mutations in the FLT3 activation loop, most commonly at amino acid D835, occur in ~8% of AML patients and their prognostic effect remains to be defined.