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Publications

Single-nucleotide variations, insertions/deletions and copy number variations in myelodysplastic syndrome during disease progression revealed by a single-cell DNA sequencing platform


Lee P, Yim R, Fung SH, Miu KK, Wang Z, Wu KC, Au L, Leung GM, Lee VH, Gill H
International Journal of Molecular Sciences Apr 2022
Abstract

Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective hematopoiesis, cytopenia, dysplasia, and clonal instability, leading to leukemic transformation. Hypomethylating agents are the mainstay of treatment in higher-risk MDS. However, treatment resistance and disease transformation into acute myeloid leukemia (AML) is observed in the majority of patients and is indicative of a dismal outcome. The residual cell clones resistant to therapy or cell clones acquiring new genetic aberrations are two of the key events responsible for drug resistance. Bulk tumor sequencing often fails to detect these rare subclones that confer resistance to therapy. In this study, we employed a single-cell DNA (sc-DNA) sequencing approach to study the clonal heterogeneity and clonal evolution in two MDS patients refractory to HMA. In both patients, different single nucleotide variations (SNVs) or insertions and deletions (INDELs) were detected with bulk tumor sequencing. Rare cell clones with mutations that are undetectable by bulk tumor sequencing were detected by sc-DNA sequencing. In addition to SNVs and short INDELs, this study also revealed the presence of a clonal copy number loss of DNMT3A, TET2, and GATA2 as standalone events or in association with the small SNVs or INDELs detected during HMA resistance and disease progression.

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Area

Heme

Institution Type

Academia

Indication / Modality

Myelodysplastic Syndrome (MDS), Acute Myleoid Leukemia (AML)

Goal of Study

Clonal Evolution, Clonal Heterogeneity, Disease Progression, Longitudinal, Therapeutic Resistance

Key Genes

IDH2, FLT3, DNMT3A, GATA2, TET2, KRAS, KIT, EZH2

PAD Project

No

Analytes Assessed

CNV, InDels, SNV

Sample Storage

Fresh Frozen

Sample Prep

Whole Cells

Sample Type

Patient Material

Tissue / Organ

Bone Marrow Aspirates

Species

Human

Panel Used

Catalog AML Panel

Proof Point Demonstrated

Better than Bulk, Clonality, Co-occurrence, Sensitivity
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