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

// Kerstin M. Kampa-Schittenhelm 1 , Wichard Vogel 1 , Irina Bonzheim 2 , Falko Fend 2 , Marius Horger 3 , Lothar Kanz 1 , Martin Soekler 1 and Marcus M. Schittenhelm 1 1 Department of Oncology, Hematology, Rheumatology, Clinical Immunology and Pulmonology, University Hospital Tubingen, Tubingen, Germany 2 Institute of Pathology and Neuropathology, Reference Center for Hematopathology, University Hospital Tubingen, Tubingen, Germany 3 Department of Diagnostic and Interventional Radiology, University Hospital Tubingen, Tubingen, Germany Correspondence to: Marcus M. Schittenhelm, email: marcus.schittenhelm@med.uni-tuebingen.de Keywords: CBF AML; KIT; tyrosine kinase inhibition; differentiation Received: September 18, 2017      Accepted: January 15, 2018      Published: January 31, 2018 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.