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G-CSF receptor (CSF3R; CD114) mutations to guide diagnosis and treatment of atypical chronic myelogenous leukemia (aCML) and chronic neutrophilic leukemia (CNL)

Patient sample studies suggest mutations in CD114 could help diagnose aCML and CNL and guide treatment decisions for the diseases. Activating mutations in CD114 were found in 16 of 27 patients with CNL or aCML, which is defined as BCR-ABL tyrosine kinase-negative CML. In patient samples, those with CD114 truncation mutations were sensitive to Sprycel dasatinib, whereas those with CD114 membrane proximal mutations were sensitive to Jakafi ruxolitinib. In one patient with CNL who had CD114 membrane proximal mutations, Jakafi normalized platelet counts and decreased white blood cell and neutrophil counts. Next steps include clinical trials to evaluate the drugs in patients who have CD114 mutations.
Incyte Corp. and Novartis AG market Jakafi, a Janus kinase-1 (JAK-1) and JAK-2 inhibitor, to treat myeloproliferative disorder.
Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. Ltd. market Sprycel, a small molecule inhibitor of BCR-ABL tyrosine kinase and Src, to treat acute lymphoblastic leukemia (ALL) and CML.

SciBX 6(22); doi:10.1038/scibx.2013.563
Published online June 6, 2013

Patent application filed; available for licensing

Maxson, J.E. et al. N. Engl. J. Med.; published online May 9, 2013;
doi:10.1056/NEJMoa1214514
Contact: Jeffrey W. Tyner, Oregon Health & Science University, Portland, Ore.
e-mail:
tynerj@ohsu.edu