NPM1 and acute myeloid leukemia: Another clinically significant mutation in AML is the internal tandem duplication (ITD) in the juxtamembrane domain of the fms-related tyrosine kinase 3 (FLT3) receptor; present in ~25% of AML patients (30% in normal karyotype AML), where ~40% of FLT3–ITD patients also comprising a NPM1 mutation.12, 21, 22 The FLT3–ITD protein is constitutively active, resulting in increased cellular proliferation; this mutation is associated with resistance to chemotherapy, increased risk for disease relapse and overall decreased survival.22