32 research outputs found
Significance Assessment of Mutations in MDS Patients Using Publicly Available Databases: A Study with 944 Samples and 6 Most Significantly Mutated Genes
Analyzing the Transcriptome Discovers up-Regulation of HOXA Genes in Patients with Myeloid Neoplasms and Isochromosome 17q and Mutations in ASXL1, SETBP1 and SRSF2
Accumulation of Somatic Mutations As a Function of Aging: A Study on 4843 TET2 Mutated Patients in Comparison to Their Respective SNP Pattern
Molecular characterization of AML with RUNX1-RUNX1T1 at diagnosis and relapse reveals net loss of co-mutations
Abstract. AML with RUNX1-RUNX1T1 fusion is a WHO entity with a favorable outcome following intensive chemotherapy. The absence of RUNX1-RUNX1T1 transcripts in remission defines complete molecular response and correlates with a superior survival. However, a significant proportion of patients still relapses and defining molecular risk factors that identify patients at diagnosis or at molecular remission that are at risk of relapse could help tailor treatment strategies for those high risk patients. Here, we analyze a cohort of 94 patients that reach a molecular remission (MR) following intensive treatment and identify 21 patients that relapse despite achieving MR. Using targeted sequencing of 63 genes implicated in hematologic malignancies we show that at diagnosis patients who relapse following MR have a higher burden of co-mutated genes than patients that do not relapse (median = 2 vs median = 0; P = 0.0156). This resulted in a relapse free survival rate of 65% vs 86% at 2 years, respectively (≥1 co-mutation vs no co-mutation, P = 0.02) with a trend for inferior overall survival (n.s.). Applying sensitive sequencing to reassess mutations at relapse in paired samples of 17/21 patients we demonstrate a net loss of co-mutations at relapse: median 2 (range 0–5) vs 1 (0–4) at diagnosis and relapse (P = 0.048). At relapse more patients had no detected co-mutation compared to diagnosis (47% vs 17%, P = 0.034). Co-mutations at diagnosis, therefore, might represent a general susceptibility of the AML clone to acquire mutations and the true nature of 2nd hit mutations that drive leukemia has to be defined for AML with RUNX1-RUNX1T1 fusion