(HealthDay News) — For patients with chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL1-negative) chronic myeloid leukemia (CML), activating mutations in the gene encoding the colony stimulating factor 3 receptor (CSF3R) are common, according to a study published in the May 9 issue of the New England Journal of Medicine.

Julia E. Maxson, Ph.D., from the Oregon Health & Science University in Portland, and colleagues used an integrated approach of deep sequencing coupled with the screening of primary leukemia cells obtained from 27 patients with CNL or atypical CML to investigate the molecular causes of these hematological cancers. Candidate oncogenes were validated using in vitro transformation assays, and drug sensitivities were evaluated.

In 59 percent of patients with CNL or atypical CML, the researchers identified activating mutations in CSF3R. The mutations segregated within two distinct regions of CSF3R, which led to distinct downstream kinase signaling (via SRC family-TNK2 or JAK kinases) and corresponding differential sensitivity to kinase inhibitors. For a patient with CNL carrying a JAK-activating CSF3R mutation, administration of the JAK1/2 inhibitor ruxolitinib correlated with marked clinical improvement.

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“Mutations in CSF3R are common in patients with CNL or atypical CML and represent a potentially useful criterion for diagnosing these neoplasms,” the authors write.

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