Myelodysplastic syndromes with ring sideroblasts (MDS-RS) and MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T) - "2021 update on diagnosis, risk-stratification, and management"

Am J Hematol. 2021 Mar 1;96(3):379-394. doi: 10.1002/ajh.26090. Epub 2021 Jan 28.


Disease overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include myelodysplastic syndromes with RS (MDS-RS) and MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).

Diagnosis: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (MDS-RS-SLD/MLD), <5% bone marrow (BM) blasts, <1% peripheral blood blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations). MDS/MPN-RS-T, now a formal entity in the MDS/MPN overlap syndromes, has diagnostic features of MDS-RS-SLD, along with a platelet count ≥450 × 109 /L and large atypical megakaryocytes.

Mutations and karyotype: Mutations in SF3B1 are seen in ≥80% of patients with MDS-RS-SLD and MDS/MPN-RS-T, and strongly correlate with the presence of BM RS; MDS/MPN-RS-T patients also demonstrate JAK2V617F (50%), DNMT3A, TET2 and ASXL1 mutations. Cytogenetic abnormalities are uncommon in both.

Risk stratification: Most patients with MDS-RS-SLD are stratified into lower risk groups by the revised-IPSS. Disease outcome in MDS/MPN-RS-T is better than that of MDS-RS-SLD, but worse than that of essential thrombocythemia (MPN). Both diseases are associated with a low risk of leukemic transformation.

Treatment: Anemia and iron overload are complications seen in both and are managed similar to lower risk MDS and MPN. Luspatercept, a first-in-class erythroid maturation agent is now approved for the management of anemia in patients with MDS-RS and MDS/MPN-RS-T. Aspirin therapy is reasonable in MDS/MPN-RS-T, especially in the presence of JAK2V617F, but the value of platelet-lowering drugs remains to be defined.

Publication types

  • Review

MeSH terms

  • Allografts
  • Anemia, Sideroblastic* / diagnosis
  • Anemia, Sideroblastic* / etiology
  • Anemia, Sideroblastic* / pathology
  • Anemia, Sideroblastic* / therapy
  • Bone Marrow / pathology
  • Cell Lineage
  • Clone Cells / pathology
  • Combined Modality Therapy
  • DNA Methylation / drug effects
  • Disease Management
  • Erythroblasts / ultrastructure
  • Ferritins / analysis
  • Hematinics / therapeutic use
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Iron Chelating Agents / therapeutic use
  • Mitochondria / chemistry
  • Mutation
  • Myelodysplastic-Myeloproliferative Diseases* / diagnosis
  • Myelodysplastic-Myeloproliferative Diseases* / genetics
  • Myelodysplastic-Myeloproliferative Diseases* / therapy
  • Phosphoproteins / genetics
  • Prognosis
  • RNA Splicing Factors / genetics
  • Risk Assessment
  • Thrombocytosis / diagnosis
  • Thrombocytosis / therapy


  • Hematinics
  • Iron Chelating Agents
  • Phosphoproteins
  • RNA Splicing Factors
  • SF3B1 protein, human
  • Ferritins