Contrasting the co-occurrence patterns of NPM1-FLT3-ITD and NPM1-RAS mouse acute myeloid leukemias by whole exome sequencing.

Mutations affecting NPM1 define the commonest subgroup of acute myeloid leukemia (AML). They frequently co-occur with mutations of FLT3, usually internal tandem duplications (ITD), and less commonly of NRAS or KRAS. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than the NPM1-RAS combination. To understand the molecular basis of these observations and contrast the potential genotype specific acquisition of additional mutations, we carried out comparative whole exome sequencing analysis (verified by amplicon specific sequencing) in AMLs derived from the two mutant knock-in mouse combinations.