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Dokumenttyp:
journal article 
Autor(en):
Gaidzik, VI; Bullinger, L; Schlenk, RF; Zimmermann, AS; Röck, J; Paschka, P; Corbacioglu, A; Krauter, J; Schlegelberger, B; Ganser, A; Späth, D; Kündgen, A; Schmidt-Wolf, IG; Götze, K; Nachbaur, D; Pfreundschuh, M; Horst, HA; Döhner, H; Döhner, K 
Titel:
RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. 
Abstract:
To evaluate frequency, biologic features, and clinical relevance of RUNX1 mutations in acute myeloid leukemia (AML).Diagnostic samples from 945 patients (age 18 to 60 years) were analyzed for RUNX1 mutations. In a subset of cases (n = 269), microarray gene expression analysis was performed.Fifty-nine RUNX1 mutations were identified in 53 (5.6%) of 945 cases, predominantly in exons 3 (n = 11), 4 (n = 10), and 8 (n = 23). RUNX1 mutations clustered in the intermediate-risk cytogenetic group (46 of 640, 7.2%; cytogenetically normal, 34 of 538, 6.3%), whereas they were less frequent in adverse-risk cytogenetics (five of 109, 4.6%) and absent in core-binding-factor AML (0 of 77) and acute promyelocytic leukemia (0 of 61). RUNX1 mutations were associated with MLL-partial tandem duplications (P = .0007) and IDH1/IDH2 mutations (P = .03), inversely correlated with NPM1 (P< .0001), and in trend with CEBPA (P = .10) mutations. RUNX1 mutations were characterized by a distinct gene expression pattern; this RUNX1 mutation-derived signature was not exclusive for the mutation, but also included mostly adverse-risk AML [eg, 7q-, -7, inv(3), or t(3; 3)]. RUNX1 mutations predicted for resistance to chemotherapy (rates of refractory disease 30% and 19%, P = .047, for RUNX1-mutated and wild-type patients, respectively), as well as inferior event-free survival (EFS; P< .0001), relapse-free survival (RFS, P = .022), and overall survival (P = .051). In multivariable analysis, RUNX1 mutations were an independent prognostic marker for shorter EFS (P = .007). Explorative subgroup analysis revealed that allogeneic hematopoietic stem-cell transplantation had a favorable impact on RFS in RUNX1-mutated patients (P< .0001).AML with RUNX1 mutations are characterized by distinct genetic properties and are associated with resistance to therapy and inferior outcome. 
Zeitschriftentitel:
J Clin Oncol 
Jahr:
2011 
Band / Volume:
29 
Heft / Issue:
10 
Seitenangaben Beitrag:
1364-72 
Sprache:
eng 
Print-ISSN:
0732-183X 
TUM Einrichtung:
III. Medizinische Klinik und Poliklinik