title: Chronic neutrophilic leukemia 2016: Update on diagnosis, molecular genetics, prognosis, and management.
abstract: Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥25 × 10(9) /L (of which >80% are neutrophils) and with <10 and <1% circulating immature granulocytes and blasts, respectively without dysplasia, clinical, or molecular criteria for other myeloproliferative disorders, nor an identifiable cause for physiologic neutrophilia in the absence of markers of myeloid clonality. Such a pathogenic clonal marker has now been identified as a somatic activating mutation of CSF3R, most commonly CSF3R T618I, thus demanding revision of the current WHO diagnostic classification to include the molecular criterion of mutated CSF3R. The clinical presentation, disease course and prognosis of CSF-R mutated CNL have been recently outlined. Co-operative mutations in SETBP1 and ASXL1 appear to be of prognostic significance and correlate with disease progression. Advances in the understanding of the molecular pathogenesis of CNL, have not yet fully translated into satisfactory therapeutic strategies, but the foundations for these are strengthening. Am. J. Hematol. 91:342-349, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota, 55905.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Elliott
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota, 55905.
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015467:Leukemia, Neutrophilic, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C473949:ASXL1 protein, human; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C425066:SETBP1 protein, human