TGF β1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia.

TGFβ1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia. Haematologica. 2018 May 17;: Authors: Geyh S, Rodríguez-Paredes M, Jäger P, Koch A, Bormann F, Gutekunst J, Zilkens C, Germing U, Kobbe G, Lyko F, Haas R, Schroeder T Abstract Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia revealing a specific molecular signature of genes commonly deregulated in myelodysplastic syndromes and acute myeloid leukemia. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level. Further analysis identified TGFβ1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to TGFβ1 healthy mesenchymal stromal cells adopted functional deficits and a phenotype reminiscent of that observed in patient-derived stromal cells. These suppressive effects of TGFβ1 on stromal cell functionality were abrogated by SD-208, an...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research