Inzidenz und prognostische Bedeutung von RUNX1 Mutationen bei Patienten mit akuter myeloischer Leukämie (AML) und normalem Karyotyp

We examined the incidence and prognostic impact of RUNX1 mutations in karyotypical normal patients with acute myeloid leukemia (CN-AML). Finally we analyzed samples from 538 patients (age 16 to 60 years) for RUNX1 mutations. Thirty-nine RUNX1 mutations were identified in 34 (6,4%) patients. All of the mutations were localized heterozygote. The mutations clustered predominantly in exons 3 (n=9), 4 (n=5), 5 (n=2), and 8 (n=19). Exon 3-5 encodes the RH-domain. RUNX1 mutations were associated with MLL-partial tandem duplications (P =.0003), inversely correlated with NPM1 (P<.001) and in trend with CEBPA (P=.10) mutations. RUNX1-mutated patients showed a resistance to chemotherapy including higher rates of refractory disease [RUNX1mut 31% versus RUNX1wt 15% (P=.05)] and in trend lower rates of complete remissions [RUNX1mut 65% versus RUNX1wt 78% (P=.09)] in comparison to the wild-type patients. Furthermore RUNX1-mutated patients showed a significant inferior event-free survival [RUNX1mut 10% versus RUNX1wt 34% (P<.0001)]. In conclusion CN-AML with RUNX1 mutations are characterized by distinct genetic properties and are associated with resistance to therapy and inferior outcome