Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing
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.
|Keywords||Bone marrow mesenchymal stromal cells, Genetic variants, Myeloid malignancies, Targeted deep sequencing|
|Persistent URL||dx.doi.org/10.1016/j.leukres.2017.09.008, hdl.handle.net/1765/108648|
|Journal||Leukemia Research: clinical and laboratory studies|
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