Chronic neutrophilic leukemia. Issue 2 (March 2015)

• Record Type: Journal Article
• Authors: Tefferi, Ayalew; Elliott, Michelle; Pardanani, Animesh
• Is Part Of: Current opinion in hematology. Volume 22:Issue 2(2015:Mar.)
• Publication Date: 2015-03
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1097/MOH.0000000000000114
• Languages: English
• ISSNs: 1065-6251

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Purpose of review</title> <p>Chronic neutrophilic leukemia (CNL) is a rare <italic>BCR-ABL1</italic>-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.</p> </sec> <sec> <title>Recent findings</title> <p>In 2013, membrane-proximal <italic>CSF3R</italic> mutations, most frequently <italic>CSF3R</italic>T618I, 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 <italic>CSF3R</italic>-mutated CNL also expressed other mutations, such as <italic>SETBP1</italic> and <italic>ASXL1</italic>, which might be prognostically detrimental. Laboratory studies revealed that <italic>CSF3R</italic>T618I 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 <italic>CSF3R</italic>-mutated CNL.</p> </sec> <sec> <title>Summary</title> <p>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.</p> </sec> </abstract>