Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management

Abstract

Disease Overview and Diagnosis: Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of 25 x 10 9 /L of which 80% are neutrophils, with < 10% circulating neutrophil precursors with blasts rarely observed. In addition, there is no dysplasia, nor clinical or molecular criteria for other myeloproliferative neoplasms.Update on Diagnosis: Previously the diagnosis of CNL was often as one of exclusion based on no identifiable cause for physiologic neutrophilia in patients fulfilling the aforementioned criteria. The 2016 WHO classification now recognizes somatic activating mutations of CSF3R (most commonly CSF3RT618I) as diagnostic, allowing for an accurate diagnosis for the majority of suspected cases through molecular testing. These mutations are primary driver mutations, accounting for the characteristic clinical phenotype and potential susceptibility to molecularly targeted therapy.Risk Stratification: Concurrent mutations, common to myeloid neoplasms and their precursor states, most frequently in SETBP1 and ASXL1, are frequent and appear to be of prognostic significance. Although data are evolving on the full genomic profile, the rarity of CNL has delayed complete understanding of its full molecular pathogenesis and individual patient prognosis.

Gene coexpression network analysis revealed biomarkers correlated with blast cells and survival in acute myeloid leukemia

“…known to regulate the production, differentiation, and function of granulocytes (23). Mutations in this gene are frequently present in patients with chronic neutrophilic leukemia (CNL) and can be used as accurate diagnostic markers for CNL (24). Mutations in CSF3R are rare in AML and have been reported to highly overlap with CEBPα mutations in AML patients, which predicts a poor outcome (25,26).…”

Update on the classification of myeloid neoplasms: The 2016 revised World Health Organization classification of hematopoietic and lymphoid neoplasms

“…CSF3R mutations are not specific for CNL as can be found in other myeloid neoplasms, particularly in atypical chronic myeloid leukemia BCR‐ABL1 negative (aCML) . Other mutations that can occur in CNL are those affecting SETBP1, ASXL1, and even JAK2 . The presence of ASXL1 mutations confer a worse prognosis …”

Molekulare Marker zur Diagnostik myeloischer Neoplasien

“…In der aCML hingegen treten Mutationen im CSF3R-Gen deutlich seltener auf. Dafür sind für die aCML weitere entitätstypische, aber nicht -spezifische Mutationen in den Genen SETBP1 und ETNK1 beschrieben [5].…”