Genetic Landscape of Acute Myeloid Leukemia (AML) in Older Patients

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In recent years, the development of next-generation sequencing (NGS) techniques have greatly advanced our understanding of the molecular pathogenesis of AML. However, most studies on the genomic profiling of AML stem from younger adult patients. From smaller studies in older patients there is increasing evidence that the (epi)genetic profile in older patients greatly differs from that of younger patients. The specific aims of the proposed project are: Evaluation of the mutational spectrum, identification of patterns of co-mutations and mutual exclusivities in a cohort of at least 1,000 older AML patients using targeted DNA sequencing, and refinement of the genomic classification of older AML; identification of prognostic and predictive factors to treatment with hypomethylating agents, and establishment of a new genetic risk classification applicable for older patients; generation of epigenetic signatures; transcriptional profiling (RNA-seq) using the novel Oxford Nanopore technology for detecting novel fusion genes and evaluating the role of altered splicing; use of single-cell sequencing to identify heterogeneity of drug response to targeted therapies. For the project we have a unique biobank from a prospective, randomized clinical trial as well as samples from our large AMLSG BiO Registry available.