Prognostic impact of RUNX1 mutations and deletions in pediatric acute myeloid leukemia: results from the French ELAM02 study group

Abstract Better knowledge of genetic aberrations in pediatric acute myeloid leukemia is essential to adapt treatment intensity. RUNX1 mutations are well described in adult AML and known to be associated with a poor outcome. In children, first studies showed similar results but because of their low frequency, prognosis impact remains unclear. RUNX1 deletions have rarely been described. Among 386 children enrolled in the French ELAM02 trial, we observed 29 (8%) patients with RUNX1 abnormalities: 24 mutations and 5 deletions. We found no significant association with any clinical presentation. RUNX1 alteration was more likely associated with AML0 cytological subtype; often presented with normal karyotype but no rearrangement classified as good prognosis markers (KMT2A or CBF-AML). RUNX1 mutated patients had higher number of co-mutations, such as FLT3-ITD, EZH2 and BCOR mutations but were never associated with NPM1 or CEBPA. Five years EFS was 32.5% for RUNX1 mutated and deleted patients versus 61.4% for RUNX1 wild type (p=0.003), and OS was 33.6% versus 75.7% (p<0.0001), confirming the negative impact already described in literature. The association between RUNX1 abnormalities in pediatric AML with an inferior survival needs more studies to precise its place in risk stratification in order to optimize treatment intensity.