کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5527694 | 1547885 | 2017 | 6 صفحه PDF | دانلود رایگان |
- Targeted deep sequencing reveals genetic variants in hemopoietic cells and MSCs.
- MSC-specific genetic variants are rare and present at very low allele frequency.
- TET2-S1107P was found at low allelic frequency in a subset of AML patients.
Bone marrow mesenchymal stromal cells (MSCs), which support proliferation and differentiation of hematopoietic stem cells, may play a crucial role in the pathogenesis of myeloid neoplasms. To determine whether MSCs in myeloid neoplasms harbor distinct somatic mutations that may affect their function, we used a targeted gene sequencing panel containing 50 myeloid neoplasm-associated genes with coverage of â¥500. We compared the genetic alterations between MSCs and bone marrow hematopoietic (BM) cells from patients with acute leukemia (n = 5) or myelodysplastic syndrome (MDS, n = 5). Non-synonymous somatic mutations, such as DNMT3A-R882H and FLT3-D835Y, were only detected in BM cells with high allelic frequency. We found several non-synonymous genetic variants overlapping BM cells and MSCs, including TP53 and ASXL1, partially owing to the heterogenous cell fraction of MSC samples and lineage fidelity. We also found MSC-specific genetic variants with very low allelic frequency (7% to 8%), such as NF1-G2114D and NF1-G140. Further studies in large cohorts are needed to clarify the molecular properties of MSCs including age-related genetic alterations by targeted deep sequencing.
Journal: Leukemia Research - Volume 62, November 2017, Pages 23-28