Lupus anticoagulant, thrombosis, and death

Abstract

inhibitors. The possibility also exists that other mutant oncoproteins implicated in leukemogenesis, and for which specific inhibitors are not yet available, could represent additional targets for this strategy.There are, however, several questions and caveats that could clearly determine the potential of this approach. For example, it remains to be established whether the ATRA/ATO strategy targets mutant NPM1-expressing leukemia-initiating cells (stem cells) which, at least theoretically, could be responsible for disease relapse. In addition, although both cultured and primary NPM1-mutant AML cells were very susceptible to this regimen, it is less certain whether the degree of cell killing can approximate that observed in the case of APL cells. Finally, although the ATRA/ATO regimen showed some activity in patients with mutant NPM1 AML, it is generally recognized that survival benefits in this (or other) disease(s) absent objective complete responses are unlikely. In this regard, the finding that ATRA/ATO enhanced the activity of an active anti-leukemic agent (eg, daunorubicin) in mutant NPM1 AML is noteworthy and raises the possibility of a more effective future approach. Alternatively, combining the ATRA/ATO strategy with other targeted therapies, including those directed against NPM1 itself, may provide opportunities for cure in this disease, as observed in some patients with APL. Finally, extrapolation of this strategy to other AML subtypes that display different oncogenic mutant proteins represents a promising possibility and one that clearly deserves further investigation.Conflict-of-interest disclosure: The author declares no competing financial interests. n