Characterization of the molecular landscape of myelodysplastic syndromes (MDS) at diagnosis and during the progression to acute myeloid leukemia (AML) can contribute in understanding the dynamics of the disease and optimize treatment.

Mutation analysis by NGS can help to better define risk-stratification of MDS patients, in particular those in the intermediate risk group. The MDS/MPN Panel encompasses 21 genes covering genes for full exon, partial region, or hot spots depending on the locus of interest for the identification of numerous recurrent somatic disease alleles with biologic, prognostic, and therapeutic relevance.


Myelodysplastic syndromes (MDS) represents a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis resulting in an expansion of poorly differentiated hematopoietic precursors with a propensity to transform into AML. According to the International Prognostic Scoring System (IPSS) MDS patients are risk-stratified. The IPSS system combines cytogenetic, morphologic, and clinical data and classifies patients into one of five risk groups: very low, low, intermediate, high, and very high. More than 80% of patients with MDS harbor recurrent somatic mutations that have clear prognostic significance and can improve risk-stratification of MDS patients especially in the intermediate risk group. Mutations in MDS occur in genes involved in RNA splicing (e.g. SF3B1, SRSF2, U2AF1, ZRSR2), DNA methylation (i.e. DNMT3A, TET2, IDH1, IDH2); or chromatin remodeling (i.e. ASXL1, EZH2).


Myeloproliferative neoplasms (MPN) comprise a group of clonal hematopoietic stem cell disorders characterized by overproduction of one or more myeloid cell lineages. MPN patients have a tendency to transform to AML and a risk of vascular events (thrombosis). Almost all MPNs are associated with clonal abnormalities and account for two main groups: BCR-ABL1-positive chronic myeloid leukemia (CML) and the BCR-ABL1-negative MPN. The BCR-ABL1 negative MPN group encompasses essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), chronic eosinophilic leukemia (CEL), chronic neutrophilic leukemia (CNL) and MPN unclassifiable. In the absence of JAK2, CALR or MPL mutations the presence of somatic mutations in other genes (e.g. ASXL1, EZH2, TET2, IDH1, IDH2, SRSF2, and SF3B1) can possibly unravel the clonal nature of the disease.