single cell DNA sequencing of myelodysplastic syndrome during drug resistance

Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by frequent epigenetic dysregulation, ineffective hematopoiesis, cytopenia, and clonal instability leading to leukemic transformation. Patients are often treated with hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DEC) as standard therapeutic protocol but resistance followed by disease transformation into acute myeloid leukemia (AML) is common. This study employed a single cell DNA (sc-DNA) sequencing approach to detect clonal mutations in a longitudinal manner and study clonal heterogeneity and clonal evolution in two MDS patients refractory to HMA therapy. In both patients, different single nucleotide variations (SNV), insertions and deletions (INDELs) and copy number variations (CNVs) were examined and compared with bulk tumour sequencing data.