Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management. Issue 2 (30th December 2019)

• Record Type: Journal Article
• Authors: Szuber, Natasha; Elliott, Michelle; Tefferi, Ayalew
• Is Part Of: American journal of hematology. Volume 95:Issue 2(2020:Feb.)
• Page Start: 212
• Page End: 224
• Publication Date: 2019-12-30
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.25688
• Languages: English
• ISSNs: 0361-8609

Abstract

Abstract: Disease overview: Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow granulocyte hyperplasia, and frequent hepatosplenomegaly. The seminal discovery of oncogenic driver mutations in colony‐stimulating factor 3 receptor ( CSF3R ) in the majority of patients with CNL in 2013 anchored a new scientific framework, deepening our understanding of its molecular pathogenesis, providing a diagnostic biomarker, and rationalizing the use of pharmacological targeting. Diagnostic criteria: In 2016, the World Health Organization (WHO) included the presence of activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 × 10 9 /L comprising >80% neutrophils with <10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN. Disease updates: Increasingly comprehensive genetic profiling of CNL has disclosed a complex genomic landscape and additional prognostically relevant mutational combinations. Though prognostic determination and therapeutic decision‐making remain challenging, emerging data on prognostic markers and the use of newer therapeutic agents, such as JAK inhibitors, are helping to define state‐of‐the‐art management in CNL.