JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Risk stratifying MDS in the time of precision medicine.

Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by morphologic dysplasia, persistent cytopenia, and a variable risk of evolution to acute myeloid leukemia (AML). Risk stratification is crucial in a patient-centered approach to the treatment of MDS. Based on hematologic parameters and cytogenetic abnormalities, the Revised International Prognostic Scoring System is currently used for this purpose. In the past years, the use of massively parallel DNA sequencing has clarified the genetic basis of MDS and has enabled development of novel diagnostic and prognostic approaches. When conventional cytogenetics is combined with gene sequencing, more than 90% of patients are found to carry a somatic genetic lesion. In addition, a portion of patients has germline variants that predispose them to myeloid neoplasms. The recently developed International Consensus Classification of MDS includes new entities that are molecularly defined-namely, SF3B1-mutant and TP53-mutant MDS. The International Working Group for Prognosis in MDS has just developed the International Prognostic Scoring System-Molecular (IPSS-M) for MDS, which considers hematologic parameters, cytogenetic abnormalities, and somatic gene mutations. The IPSS-M score is personalized and can be obtained using a web-based calculator that returns not only the individual score but also the expected leukemia-free survival, overall survival, and risk of AML transformation. Providing an efficient risk stratification of patients with MDS, the IPSS-M represents a valuable tool for individual risk assessment and treatment decisions.

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