title: Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia.
abstract: Severe congenital neutropenia (SCN) is a heterogeneous bone marrow failure syndrome predisposing to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We studied 82 North American and Australian SCN patients enrolled in the Severe Chronic Neutropenia International Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced. There was no significant difference in the risk of MDS/AML in patients with mutant versus wild-type ELA2: the respective cumulative incidences at 15 years were 36% and 25% (P = 0.96). Patients with either mutant or wild-type ELA2 should be followed closely for leukaemic transformation.
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
authors.forename: Steven
authors.initials: S
authors.lastname: Stein
authors.forename: Elin
authors.initials: E
authors.lastname: Rodger
authors.forename: Audrey A
authors.initials: AA
authors.lastname: Bolyard
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Aprikyan
authors.forename: Mary A
authors.initials: MA
authors.lastname: Bonilla
authors.forename: Yigal
authors.initials: Y
authors.lastname: Dror
authors.forename: George
authors.initials: G
authors.lastname: Kannourakis
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Boxer
authors.forename: David C
authors.initials: DC
authors.lastname: Dale
mesh_terms: D001315:Australia / Q000453:epidemiology; D002908:Chronic Disease; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004812:Epidemiologic Methods; D020022:Genetic Predisposition to Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D019272:Leukocyte Elastase / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000235:genetics; D009503:Neutropenia / Q000151:congenital / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D011230:Precancerous Conditions / Q000151:congenital / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D019272:Leukocyte Elastase