Internuclear chromosome distribution of dysplastic megakaryocytes in myelodysplastic syndromes is dependent on the level of ploidy

Megakaryopoiesis is largely disturbed in myelodysplastic syndromes (MDS), and megakaryocytes (MKs) frequently show multinucleation. Here, we investigated dysplastic mono-, bi-, and multinuclear MKs (n = 169) of seven patients with MDS and one patient with myelodysplastic/myeloproliferative neoplasm by sequential multilocus FISH. Analysis of binuclear MKs with a combined DNA content of 4 N (n = 46) indicated a significantly even (symmetric) chromosome distribution between the two separate nuclei (p = 0.0223), which suggests bipolar spindle orientation and symmetric chromosome segregation during the first endomitotic cell cycle. In contrast, multinuclear MKs of higher ploidy (>4 N, n = 108) demonstrated a significantly uneven (asymmetric) chromosome distribution between the separate nuclei (p = 0.0248). Thus, the internuclear chromosomal distribution of dysplastic MKs depends on the level of ploidy. In addition, centrosomal aberrations were not found in dysplastic MKs. Our results indicate that megakaryocytic multinucleation in MDS originates from dysregulated endomitosis, including restoration of karyokinesis.