Traipsing Through Muddy Waters: A Critical Review of the Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) Overlap Syndromes

Myelodysplastic syndrome/Myeloproliferative neoplasms (MDS/MPNs) are molecularly complex, clinically heterogeneous diseases that exhibit proliferative and dysplastic features. Diagnostic criteria use clinical, pathologic, and genomic features to distinguish between disease entities, though considerable clinical and genetic overlap persists. MDS/MPNs are associated with a poor prognosis, save for MDS/MPN with ring sideroblasts and thrombocytosis, which can behave more indolently. The current treatment approach is risk-adapted and symptom-directed and largely extrapolated from experience in MDS or MPN. Gene sequencing has demonstrated frequent mutations involving signaling, epigenetic, and splicing pathways, which present numerous therapeutic opportunities for clinical investigation.