Clonal architecture and molecular signatures of MDS/MPN overlap syndromes. The panel on the left illustrates all 5 MDS/MPN overlap syndrome entities with corresponding specific mutational signatures. CMML has additional subcategories based on the relative enrichment of mutation types in proliferative (MPN-CMML) or dysplastic (MDS-CMML) CMML. Each entity is spatially placed according to mutation type in relation to myeloproliferative (on the right) and myelodysplastic (on bottom) features. The five mutated gene categories are represented in the left panel: epigenetic (green), signaling (pink), splicing (orange), other (purple), and transcription (blue). The panels on the right depict the influence of mutations on each MDS/MPN overlap subtype. aCML, atypical chronic myeloid leukemia; CMML, chronic myelomonocytic leukemia; CMP, common myeloid progenitor; GM, granulocytic-monocytic; JMML, juvenile myelomonocytic leukemia; MDS/MPN-RS-T, MDS/MPN-ring sideroblasts and thrombocytosis; MDS/MPN-U, MDS/MPN-unclassifiable.