Multiple distinct clones may co-exist in different lineages in myelodysplastic syndromes.

Using single nucleotide polymorphism (SNP) microarray with unfractionized bone marrow specimens, recent studies have demonstrated that multiple cytogenetically cryptic genomic aberrations, uniparental disomy (UPD) and/or copy number (CN) aberration, are present in patients with myelodysplastic syndromes (MDS). We hypothesize that various hematopoietic lineages in MDS may carry different cytogenetically cryptic genomic aberrations leading to lineage-specific manifestations of MDS. Flow cytometry sorting was performed to sort 12 MDS marrow samples into blastic, erythroid, immature myeloid and lymphoid fractions. The fractions with enough DNA underwent 250K SNP microarray analysis. Of importance, different chromosomal regions of UPD, deletions and/or gains were present in different fractions of same patients in all samples. Only small percentages (6.7%) of genomic aberrations were present in all fractions from same patients. These results suggest that multiple distinct clones may co-exist in different lineages in MDS and may contribute to cytopenias in specific lineages and the significant clinical heterogeneity observed in these patients. Further studies are warranted to confirm our findings and to investigate the lineage specific genomic lesions in MDS.

Duke Scholars

Author Ken H Young Pathology