Molecular genetics of MDS/MPN overlap syndromes

Best Pract Res Clin Haematol. 2020 Sep;33(3):101195. doi: 10.1016/j.beha.2020.101195. Epub 2020 Jul 5.

Abstract

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are a heterogenous group of myeloid malignancies hallmarked by clinicopathologic features that overlap with myelodysplastic syndromes and myeloproliferative neoplasms. Formally recognized by the World Health Organization, this group includes the entities chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN with ring sideroblasts and thrombocytosis and MDS/MPN, unclassifiable. Advancements in next generation sequencing have begun to unravel the molecular underpinnings of these diseases, identifying an array of recurrently mutated genes involved in epigenetic regulation, RNA splicing, transcription, and cell signaling. Despite molecular overlap with other myeloid malignancies, each entity displays a unique spectrum of somatic mutations supporting their unique pathobiology and clinical features. Importantly, molecular profiling is becoming an integral tool utilized in routine clinical practice. This review summarizes our current understanding of the molecular pathogenesis of overlap syndromes and details the impact of somatic mutations in diagnostic, prognostic, and therapeutic decision-making.

Keywords: Atypical chronic myeloid leukemia; Chronic myelomonocytic leukemia; Juvenile myelomonocytic leukemia; MDS/MPN; MDS/MPN unclassifiable; MDS/MPN with Ring sideroblasts and thrombocytosis; Myelodysplastic/myeloproliferative neoplasm; Overlap syndromes.

Publication types

  • Review

MeSH terms

  • Epigenesis, Genetic*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative* / diagnosis
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative* / genetics
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative* / metabolism
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative* / therapy
  • Leukemia, Myelomonocytic, Juvenile* / diagnosis
  • Leukemia, Myelomonocytic, Juvenile* / genetics
  • Leukemia, Myelomonocytic, Juvenile* / metabolism
  • Leukemia, Myelomonocytic, Juvenile* / therapy
  • Myelodysplastic Syndromes* / diagnosis
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / metabolism
  • Myelodysplastic Syndromes* / therapy
  • Thrombocytosis* / diagnosis
  • Thrombocytosis* / genetics
  • Thrombocytosis* / metabolism
  • Thrombocytosis* / therapy