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 for Chronic Neutrophilic Leukemia (CNL)
1. Peripheral blood (PB) white blood cell (WBC) ≥25 x 109/L
- Segmented neutrophils plus band forms ≥80% of WBC
- Neutrophil precursors (promyelocytes, myelocytes, and metamyelocytes) <10% of WBC
- Myeloblasts rarely observed
- Monocyte count <1 x 109/L
- No dysgranulopoiesis
2. Hypercellular bone marrow (BM)
- Neutrophil granulocytes increased in percentage and number
- Neutrophil maturation appears normal
- Myeloblasts <5% of nucleated cells
3. Not meeting WHO criteria for BCR-ABL1, CML, PV, ET, or PMF
4. No rearrangement of PDGFRA, PDGFRB, or FGFR1, or PCM1-JAK2
5. Presence of CSF3R T618I or other activating CSF3R mutation
or
In the absence of a CSFR3R mutation, persistent neutrophilia (at least 3 mo), splenomegaly and no identifiable cause of reactive neutrophilia including absence of a plasma cell neoplasm or, if present, demonstration of clonality of myeloid cells by cytogenetic or molecular studies.
References:
- Szuber N, Elliott M, Tefferi A. Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management. Am J Hematol. 2020 Feb;95(2):212-224. [Medline]
- Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. [Medline]
Created Apr 22, 2021.
