Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.

Clonal evolution and changes in two AML patients detected with a novel single-cell DNA sequencing platform

Xu, L. et. al
Stanford University, Palo Alto, CA
Scientific Reports (2019)

Next-generation sequencing (NGS) is used to detect gene variants in genetically complex cell populations of cancer patient samples. Traditional bulk analysis can only provide average variant allele frequencies of the targeted genes across all sampled cells. It fails to resolve mutational co-occurrences and may miss rare cancer cells. Genome analysis at the single cell level offers the opportunity to more fully resolve clonal architecture. Peripheral blood mononuclear cells were sampled from acute myeloid leukemia patients longitudinally and single-cell DNA sequencing libraries were generated with a novel droplet-based microfluidics approach. Molecular profiling of single nucleotide variants across thousands of cells revealed genetic chimerism in patients after bone marrow transplantation (BMT). Importantly, hierarchical clustering analysis of single nucleotide variants (SNVs) uncovered a distinct oncogenic clone of cells carrying mutated tumor-suppressor and/or oncogene(s). This novel single-cell DNA sequencing approach enabled precise monitoring of engraftment and revealed clonal evolution of oncogenic cells during the progression and treatment of the disease.

Biological and clinical significance of dysplastic hematopoiesis in patients with newly-diagnosed multiple myeloma
Maia, C. et al
Distinct genetic pathways define pre-leukemic and compensatory clonal hematopoiesis in Shwachman-Diamond syndrome
Kennedy, A, L. et al
Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML
Choe, S. et. al
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML
DiNardo, C. D. et. al