Morphologic findings and mutational profiles of myelodysplastic neoplasms with normal versus abnormal karyotype.

Abstract

Myelodysplastic syndromes are clonal bone marrow failure disorders demonstrating variable degrees of cytopenias, morphologic dysplasia, and risk of progression to acute myeloid leukemia.We hypothesized that MDS with a normal karyotype (NK) would exhibit a unique mutational or morphologic signature.We investigated the morphologic features and genetic profiles of 89 patients with myelodysplastic syndrome (MDS), including 42 with a NK and 47 with an abnormal karyotype (non-NK). We used next-generation sequencing (NGS) to detect pathogenic variants and performed morphologic review by two independent hematopathologists in a blinded manner with a nested set of 43 control cases.NK and non-NK cases showed similar levels of dysplasia in granulocytes and erythroids, but non-NK cases showed significantly more dysplasia in megakaryocytes (P?=?0.037). The mutational burden was similar between NK and non-NK cases. TET2 and SF3B1 mutations were more frequent in NK cases (P?=?0.029 and P?=?0.013, respectively), and TP53 mutations were more frequent in non-NK cases (P?=?0.007). Overall, higher mutational burden was associated with higher levels of megakaryocyte dysplasia (P?=?0.003), but there was no association with granulocytic or erythroid dysplasia. Cases with STAG2 mutations were associated with higher overall megakaryocyte dysplasia (P?=?0.0016) and proportion of megakaryocytes with separate nuclear lobes (P?

View details for DOI 10.1007/s12308-026-00686-6

View details for PubMedID 41721060

View details for PubMedCentralID 10401750