Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia

Br J Haematol. 2008 Jan;140(2):210-3. doi: 10.1111/j.1365-2141.2007.06897.x. Epub 2007 Nov 20.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia / epidemiology
  • Chronic Disease
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Epidemiologic Methods
  • Genetic Predisposition to Disease
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukocyte Elastase / genetics*
  • Mutation*
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / genetics
  • Neutropenia / congenital
  • Neutropenia / drug therapy
  • Neutropenia / epidemiology
  • Neutropenia / genetics*
  • Precancerous Conditions / congenital
  • Precancerous Conditions / drug therapy
  • Precancerous Conditions / epidemiology
  • Precancerous Conditions / genetics*
  • United States / epidemiology

Substances

  • Granulocyte Colony-Stimulating Factor
  • Leukocyte Elastase