Dasatinib overrides the differentiation blockage in a patient with mutant-KIT D816V positive CBFβ-MYH11 leukemia.

Dasatinib overrides the differentiation blockage in a patient with mutant-KIT D816V positive CBFβ-MYH11 leukemia.

Oncotarget. 2018 Feb 20;9(14):11876-11882

Authors: Kampa-Schittenhelm KM, Vogel W, Bonzheim I, Fend F, Horger M, Kanz L, Soekler M, Schittenhelm MM

Abstract
Activating KIT D816V mutations are frequently found in CBF AML, which predicts for an unfavorable outcome. Dasatinib is a potent inhibitor of wildtype and mutant-KIT isoforms - including D816V. We now provide proof of antileukemic efficacy in a patient with relapsing mutant-KIT D816V CBF AML. Importantly, this effect is mediated via overriding the differentiation blockage of the leukemia clone. In addition, we show that dasatinib is capable to induce pulmonary differentiation syndrome - and therefore needs close monitoring of patients under therapy.

PMID: 29545943 [PubMed]

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