Co-occurrence of -TKD and mutations defines a highly favorable prognostic AML group.

Although internal tandem duplication (ITD) mutations in acute myeloid leukemia (AML) confer an adverse prognosis, co-occurrence with a nucleophosphomin () mutation partially improves response and survival outcomes. In contrast, simultaneous and tyrosine kinase domain (TKD) mutations were reported to improve response over that of an isolated mutation in one as yet unverified report. To validate this, we explored the impact of the co-occurrence of -TKD and mutations on clinical outcomes. Study populations included 21 patients (8%) with -TKD mutated, 18 patients (7%) with -TKD-only-mutated, 117 patients (44%) with -only-mutated, and 107 patients (41%) with -ITD-mutated AML. Compared with -only-mutated AML, -TKD/ double mutation status was associated with a significantly superior relapse-free survival (median, not reached vs 18.3 months; = .03) and a trend toward improved overall survival (OS). The presence of -TKD/ double mutation status was an independent positive predictor in multivariable analysis. Allogeneic stem cell transplant did not improve outcomes in the -TKD/ cohort. Consistent with historical data, the co-mutation status defined a highly favorable prognostic group characterized by high response rates and prolonged disease-free and OS. These study findings substantiate previous data describing this intriguing paradoxical cooperative effect. Our results emphasize the need for elucidating the mechanistic links between -TKD and in future molecular and murine model studies.