The Association of Mutations in RUNX1 and CSF3R with the Development of Leukemia in Severe Congenital Neutropenia: A unique pathway in leukemogenesis
J Skokowa, D Steinemann, C Zeidler, V Makaryan, R Beekman, M Klimiankou, M Ünalan, S Kandabarau, S Schnittger, A Kohlmann, MG Valkhof, R Hoogenboezem, G Göhring, B Schlegelberger, M Stanulla, P Vandenberghe, J Donadieu, IP Touw, DC Dale, K Welte · Klinische Pädiatrie · 2013 · Heft 05
Bibliografische Angaben
Zusammenfassung
Severe congenital neutropenia (CN) is a rare inherited disorder of hematopoiesis with a approx. 20% risk to evolve to acute myeloid leukemia. We investigated the patterns of acquisition of leukemia-associated-mutations in 31 CN patients developing leukemia using DNA deep sequencing. We found that 20 of the 31 patients (64.5%) demonstrated mutations within RUNX1. Of the 20 patients with RUNX1 mutations, 19 harboured CN-associated mutations: ELANE (11), ELANE+GFI1 (1), WAS (3), HAX1 (3) and G6PT (SLC37A4) (1). The majority of patients with RUNX1 mutations (75%) harboured cooperating acquired CSF3R mutations. Other…
