Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing
Leukemia Research: clinical and laboratory studies , Volume 62 p. 23- 28
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 ≥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.
|Bone marrow mesenchymal stromal cells, Genetic variants, Myeloid malignancies, Targeted deep sequencing|
|Leukemia Research: clinical and laboratory studies|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Azuma, K. (Kenko), Umezu, T. (Tomohiro), Imanishi, S. (Satoshi), Asano, M, Yoshizawa, S. (Seiichiro), Katagiri, S. (Seiichiro), … Ohyashiki, J.H. (Junko H.). (2017). Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing. Leukemia Research: clinical and laboratory studies, 62, 23–28. doi:10.1016/j.leukres.2017.09.008