Chronic neutrophilic leukemia 2014: Update on diagnosis, molecular genetics, and management

Abstract

Disease Overview: Chronic neutrophilic leukemia (CNL) is a myeloproliferative neoplasm characterized by sustained, mature neutrophilic leukocytosis, splenomegaly, and bone marrow granulocytic hyperplasia. Diagnosis: Key diagnostic criteria include leukocytosis of >25 × 109/l (of which >80% are neutrophils) with <10% and <1% circulating immature granulocytes and myeloblasts, respectively. There should be no dysplasia, monocytosis, molecular evidence of BCR‐ABL1, PDGFRA, PDGFRB, or FGRF1 rearrangements and no identifiable cause for physiologic neutrophilia or, if present, demonstration of myeloid clonality. Developments in Molecular Genetics: Recently, CNL has been shown to be specifically driven by somatic activating mutations of CSF3R, most commonly CSF3R T618I. As such, the diagnosis of CNL will no longer be one of exclusion only, and revision of the current WHO classification is anticipated to include the molecular criterion of mutated CSF3R. Am. J. Hematol. 89:651–658, 2014. © 2014 Wiley Periodicals, Inc.

Diagnosis, complications and management of chronic neutrophilic leukaemia: A case report

“…These mutations have been identified in myeloproliferative disorders, but only JAK2 has been reported in CNL (11)(12)(13). Recently, Maxson et al reported the association between receptor for colony-stimulating factor 3 (CSF3R) mutations and CNL and atypical CML (14), which could be a promising marker of the disease (15). In the present case, the karyotype was normal, but nearly 10% of CNL cases are associated with cytogenetic abnormalities, including trisomy 8, 9, 21 and deletion of 11(q), 12(p), 17(p) and 20(q), the latter possibly being associated with a more favorable prognosis (16)(17)(18).…”

An update on BCR-ABL1-negative myeloproliferative neoplasms

“…42 The JAK2 V617F mutation has also been reported in CNL but its significance is unclear. 43 Neutrophilic progression in a case of PV mimicking CNL has been described, emphasizing the need for careful work-up in complex cases. 44 CSF3R mutations have also been reported in hereditary chronic neutrophilia.…”

“…44 CSF3R mutations have also been reported in hereditary chronic neutrophilia. 43 There is a well established association between neutrophilia and plasma cell neoplasia. Granulocyte-colony stimulating factor-producing myeloma has been described, with clinical manifestations mimicking CNL.…”

“…38 Progression in CNL is not as well defined as in the more common MPN categories but therapy-resistant progressive neutrophilia, thrombocytopenia, splenomegaly, clonal evolution and myeloid blast crisis are recognized. 43 Revision of the current WHO classification is expected to include the molecular criterion of mutated CSF3R in the diagnostic criteria for CNL. 43,45 A recent proposal principally includes peripheral blood leucocytosis !13 Â 10 9 /litre, >80% neutrophils or bands and the presence of CSF3R T618I or other membrane proximal CSF3R mutations and lack of dysgranulopoiesis.…”

“…43 Revision of the current WHO classification is expected to include the molecular criterion of mutated CSF3R in the diagnostic criteria for CNL. 43,45 A recent proposal principally includes peripheral blood leucocytosis !13 Â 10 9 /litre, >80% neutrophils or bands and the presence of CSF3R T618I or other membrane proximal CSF3R mutations and lack of dysgranulopoiesis. There must be no monocytosis, molecular evidence of BCR-ABL-1, PDGFRA, PDGFRB, or FGRF1 rearrangement.…”