Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia.
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.
Rosenberg
Philip S
PS
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
Alter
Blanche P
BP
Link
Daniel C
DC
Stein
Steven
S
Rodger
Elin
E
Bolyard
Audrey A
AA
Aprikyan
Andrew A
AA
Bonilla
Mary A
MA
Dror
Yigal
Y
Kannourakis
George
G
Newburger
Peter E
PE
Boxer
Laurence A
LA
Dale
David C
DC
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
D016179:Granulocyte Colony-Stimulating Factor; D019272:Leukocyte Elastase