NGS per le Leucemie Acute Mieloidi e le MDS

Acute myeloid leukemias (AMLs) and myelodysplastic syndromes (MDSs) are clonal disorders of hematopoietic stem cells that mainly affect adults. Either exogenous or genetic factors are recognized to produce de-novo cell DNA damages and to increase the susceptibility to acquire primary genetic lesions, which in turn can induce an accumulation of secondary genetic aberrations leading to a dysregulation of cell proliferation and differentiation. In the last decade, significant progresses have been made in the recognition of the molecular pathways regulating the proliferation, differentiation and apoptosis of normal hematopoietic stem cell and of leukemogenetic mechanisms leading to MDS/AML development. About 40% of AML patients do not show any alteration by using the standard chromosome binding analysis (CBA) or fluorescent in-situ hybridization (FISH). Therefore, the best tool for molecular and genomic characterization of AMLs and MDSs is now the Next Generation Sequencing (NGS) that allows to evaluate a large number of genes with high precision and sensitivity, at costs relatively low. In the last years, more genetic mutations in AML and MDS patients have been detected and these mutations may serve as potential markers to extend the prognostication in these disease. Moreover, new knowledges about the recurrent gene mutations and their clinical implications in AML patients has been achieved. Different studies demonstrated that clinical NGS sequencing frequently detects mutations in genes associated with myeloid disease (~70%). NGS allows to perform a descriptive analysis of the clonal evolution of patients with AML and MDS. So, it is possible compare the clonal composition at the time of diagnosis and of resistance/relapse. In the present research group NGS is applied in order to perform discovery of new genes involved in leukemogenesis and in the predisposition to AML/MDS. Moreover, the group aims to assess a workflow based on different innovative molecular biology tools in order to improve the diagnosis, the prognostication and the risk assessment of AML/MDS patients.