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Dysplasia and proliferation are histological properties that can be used to diagnose and categorize myeloid tumors in myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). However, these conditions are not exclusive, and overlap between them leads to another classification, MDS/MPN. As well as phenotype continuity, these three conditions may have genetic relationships that have not yet been identified. This study aimed to obtain their mutational profiles by meta-analysis and explore possible similarities and differences. We reviewed screening studies of gene mutations, published from January 2000 to March 2020, from PubMed and Web of Science. Fifty-three articles were eligible for the meta-analysis, and at most 9,809 cases were involved for any gene. The top mutant genes and their pooled mutation rates were as follows:  SF3B1  (20.2% [95% CI 11.6–30.5%]) in MDS,  TET2  (39.2% [95% CI 21.7–52.0%]) in MDS/MPN, and  JAK2  (67.9% [95% CI 64.1–71.6%]) in MPN. Subgroup analysis revealed that leukemic transformation-related genes were more commonly mutated in high-risk MDS (MDS with multilineage dysplasia and MDS with excess blasts) than that in other MDS entities. Thirteen genes including  ASXL1, U2AF1, SRSF2, SF3B1 , and  ZRSR2  had significantly higher mutation frequencies in primary myelofibrosis (PMF) compared with essential thrombocythemia and polycythemia vera; this difference distinguished PMF from MPN and likened it to MDS. Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia were similar entities but showed several mutational differences. A heat map demonstrated that juvenile myelomonocytic leukemia and MDS/MPN with ring sideroblasts and thrombocytosis were two distinct entities, whereas MDS/MPN-unclassifiable was closest to high-risk MDS. Such genetic closeness or difference reflected features in the pathogenesis, diagnosis, treatment, and progression of these conditions, and could inspire future genetic studies.

frontiers in oncology

Comparison and Implications of Mutational Profiles of Myelodysplastic Syndromes, Myeloproliferative Neoplasms, and Myelodysplastic/Myeloproliferative Neoplasms: A Meta-Analysis