Novel Tyrosine Kinase Mutation Discovered in CNL and CML

Chronic neutrophilic leukemia (CNL) and Philadelphia chromosome–negative atypical chronic myeloid leukemia (CML) are rare myeloproliferative disorders. To identify the previously unknown genetic basis of these leukemias, investigators used genomics methodologies to screen for tyrosine kinase (TK) mutations and other mutations in primary patient blood and marrow samples.

Mutations in the CSF3R gene were identified in 16 (59%) of 27 patients. Although a variety of mutations were described, all served to activate TK signaling and downstream targets, including JAK family kinases and SRC family TNK2 kinases. Of note, CSF3R mutation was associated with responsiveness to the JAK inhibitor ruxolitinib or dasatinib, an inhibitor of SRC kinases in add…