Transforming growth factor β1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia

Haematologica
S GeyhThomas Schroeder

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 and found a specific molecular signature of genes commonly deregulated in these disorders. 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 transforming growth factor β1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to transforming growth factor β1, healthy mesenchymal stromal cells developed functional deficits and adopted a phenotype reminiscent of that observed in patient-derived stromal cells. These suppressive effects of transforming growth factor β1 on stromal cell functionality were abrogated by SD-208, an established inhibitor of transforming growth fa...Continue Reading

Citations

Jan 24, 2019·Blood·Eline Pronk, Marc H G P Raaijmakers
May 5, 2020·The Journal of Clinical Investigation·Alexander WaclawiczekDominique Bonnet
Jan 17, 2020·British Journal of Haematology·Yajing JiangTianxiang Pang
May 24, 2020·Journal of Clinical Medicine·Alice PievaniMarta Serafini
Feb 16, 2021·Pharmacology & Therapeutics·Dingyu HuJi Zhang
May 1, 2021·International Journal of Molecular Sciences·Erica DanderGiovanni Cazzaniga
Jul 3, 2021·Journal of Clinical Medicine·Suncica Kapor, Juan F Santibanez

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Methods Mentioned

BETA
MDS
light microscopy
flow
FCS
X-ray
PCR
flow cytometry

Software Mentioned

Prism
Cuffdiff
FCS Express
pheatmap
DESeq2
Ingenuity analysis
GraphPad
Tophat2
FactoMineR
R

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