Purpose of review
Chronic
neutrophilic leukemia (CNL) is a rare
BCR-ABL1-negative myeloid malignancy that is characterized by mature granulocytosis without dysgranulopoiesis. Differential diagnosis of CNL includes reactive or secondary granulocytosis and other myeloid neoplasms, such as atypical chronic myeloid
leukemia (aCML) and chronic myelomonocytic
leukemia (CMML). Herein, we focus on recently described mutations in CNL and their impact on diagnosis, prognosis and treatment.
Recent findings
In 2013, membrane-proximal
CSF3R mutations, most frequently
CSF3RT618I, were described in CNL and aCML. Subsequent studies confirmed the presence of such mutations in nearly all patients with CNL but not in aCML. Furthermore, the majority of the patients with
CSF3R-mutated CNL also expressed other mutations, such as
SETBP1 and
ASXL1, which might be prognostically detrimental. Laboratory studies revealed that
CSF3RT618I induced JAK inhibitor-sensitive activation of JAK-STAT and CNL-like disease in mice. Case reports have indicated palliative but not disease-modifying activity of JAK inhibitor therapy in
CSF3R-mutated CNL.
Summary
CNL is now a morphologically and molecularly defined myeloid malignancy, and no longer a diagnosis of exclusion. The identification of CNL-specific molecular markers provides a much needed pathogenetic insight and also offers the opportunity to revise current diagnostic criteria and identify prognostic biomarkers and potential drug targets.
