SIDEBAR: New Insights into Treatment for Two Types of Leukemia 

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The combination of functional and genomic screens has allowed us to accelerate the identification of oncogenes, as well as drug sensitivity that corresponds with those oncogenes. In the present study, we found that CSF3R mutations define chronic neutrophilic leukemia and atypical chronic myeloid leukemia—two forms of leukemia that were not previously associated with any defining genetic lesions.

Through our integrated approach of functional screening and genomic analysis on primary patient samples, we were able to demonstrate that CSF3R membrane-proximal mutations confer sensitivity to JAK kinase inhibitors, while CSF3R truncation mutations confer sensitivity to SRC inhibitors. This mechanism of differential drug sensitivity by two types of mutations within the same gene was significantly accelerated by the integrated functional genomic screening paradigm.

Our next step will be to apply this functional genomic pipeline to other leukemias to match other genetic drivers with targeted therapies. ■

Disclosure: Drs. Maxson and Tyner reported no potential conflicts of interest.

Dr. Maxson is Postdoctoral Fellow and Dr. Tyner is Assistant Professor, Knight Cancer Institute and Cell & Developmental Biology Department, Oregon Health and Science University, Portland.