Study Reveals Cytogenetically Driven Disruption of Myeloid Cell Maturation in MDS

A study elucidated the impact of accumulated abnormalities on myelodysplastic syndromes (MDS) and the severity of the disease. The results were published in Cytometry. Part B, Clinical Cytometry.

Researchers collated bone marrow specimens from 16 patients with cytogenetic abnormalities, and flow cytometrically were sorted into three myeloid populations: progenitors, immature myeloid cells, and mature myeloid cells. Fluorescence in situ hybridization (FISH) analysis was performed on each specimen to discern the distribution of chromosomal abnormalities.

The study results revealed three distinct distributions of cytogenetic abnormalities across myeloid maturation, each of which corresponded to specific cytogenetic abnormalities. In Group 1, the researchers observed continuous distribution across all maturational stages, and patients had a single cytogenetic aberration that was associated with good-to-intermediate prognosis. In Group 2, the results found an accumulation of abnormalities in immature cells; this group contained patients with high-risk monosomy 7. Group 3 displayed abnormalities defining the founding clone equally distributed across maturational stages, while subclonal abnormalities were enriched in progenitor cells. This group contained patients with multiple, non-monosomy 7, abnormalities with evidence of clonal evolution, the researchers noted.

“Our findings demonstrate that low-risk abnormalities occurring in the founding clone display a markedly different disease etiology, with respect to myeloid maturation, than monosomy 7 or abnormalities acquired in subclones, which result in a disruption of myeloid cell maturation in MDS,” the researchers concluded.