Myelodysplastic Syndromes (MDS)

Overview

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and bone marrow dysplasia. MDS sits at level 3 in OncoTree under the myeloid neoplasm with myelodysplastic features (MNM) branch. Diagnosis relies on integration of morphologic dysplasia with molecular profiling; recurrent mutations in spliceosomal, epigenetic, and cohesin complex genes define clinically distinct subtypes.

Cohorts in the corpus

  • Discovery cohort: 80 MDS bone marrows (Brigham and Women’s Hospital, 2013–2014) sequenced with a 50-gene targeted panel. PMID:21909114
  • Enrichment cohort: 155 myeloid neoplasms with myelodysplastic features (2014–2018) sequenced with a 95-gene clinical panel, enriched for combinations of STAG2, RUNX1, SRSF2, ASXL1, and SETBP1 mutations. PMID:21909114

Recurrent alterations

  • STAG2 — somatic loss-of-function mutations; independently associated with separated megakaryocyte nuclei (OR 32.4 discovery, OR 5.54 enrichment; P<0.001), abnormal myeloid nuclear segmentation (OR 3.04; P=0.016), and myeloid cell hypogranulation (OR 6.48; P<0.001) in MDS bone marrows. PMID:21909114
  • ASXL1 — somatic mutations independently associated with separated megakaryocyte nuclei (enrichment cohort multivariable OR 2.55; P=0.018). PMID:21909114
  • SF3B1 — mutations associated with ring sideroblasts and erythroid dysplasia. PMID:21909114
  • TP53 — mutations associated with erythroid dysplasia. PMID:21909114
  • SRSF2 — association with megakaryocyte dysplasia confounded by co-mutation with STAG2. PMID:21909114
  • RUNX1 — mutations associated with megakaryocytic dysplasia in univariate analysis. PMID:21909114
  • SETBP1 — mutations independently associated with abnormal granulocytic nuclear segmentation (discovery cohort OR 12.2; P=0.042). PMID:21909114
  • CALR exon 9 frameshift indels were detected in 10/120 (8%; 95% CI 4-15) MDS cases in a Sanger sequencing screen of 1,345 hematologic cancers, making MDS the non-MPN cancer type with the highest CALR mutation prevalence in this study. PMID:24325359
  • The chromatin–spliceosome AML subgroup (18% of 1540 AMLSG trial patients) shares RNA-splicing and chromatin-modifier mutations with high-risk MDS and myeloproliferative neoplasms, suggesting shared evolutionary trajectories and possible reorganization of acute/chronic myeloid disease boundaries PMID:27276561.
  • In the 10-day decitabine trial (N=116, Washington University), transfusion-dependent MDS patients were enrolled alongside AML; TP53 mutations showed a trend toward decreased survival in the MDS subset (P=0.08, underpowered); all 9 evaluable relapses arose from preexisting subclones detected pre-therapy PMID:27959731.

Subtypes

  • Morphologic-molecular subtypes can be partially defined by gene-dysplasia correlations: STAG2/ASXL1 mutations associate with megakaryocytic dysplasia (separated nuclei); SF3B1 mutations associate with ring sideroblasts; TP53 mutations associate with erythroid dysplasia. PMID:21909114

Therapeutic landscape

No direct therapeutic implications were demonstrated in the corpus studies for MDS to date.

Sources

  • PMID:21909114 — STAG2 and ASXL1 mutations correlate with specific bone marrow dysplastic morphology in MDS (Tokyo/BWH cohorts, n=235 total).

This page was processed by crosslinker on 2026-05-09. - PMID:24325359

This page was processed by crosslinker on 2026-05-09. - PMID:27276561 — Papaemmanuil et al. 2016, NEJM. Chromatin–spliceosome AML overlaps mutationally with high-risk MDS.

This page was processed by entity-page-writer on 2026-05-15. - PMID:27959731

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