Loading...
High BM plasma S100A8/A9 is associated with a perturbed microenvironment and poor prognosis in myelodysplastic syndromes
Wang, Y. H. Lin, C. C. Yao, C. Y. Amaral, Fabio Yu, S. C. Kao, Chein-Jun Shih, P. T. Hou, H. A. Chou, W. C. Tien, H. F.
Wang, Y. H.
Lin, C. C.
Yao, C. Y.
Amaral, Fabio
Yu, S. C.
Kao, Chein-Jun
Shih, P. T.
Hou, H. A.
Chou, W. C.
Tien, H. F.
Citations
Altmetric:
Abstract
S100A8/A9 is a proinflammatory protein and plays an essential role in the pathogenesis of myelodysplastic syndromes (MDS) via the S100A8/A9-Toll-like receptors axis. While S100A8/A9 levels have been used as biomarkers in many inflammatory diseases, their clinical relevance has not been conclusively resolved in MDS. To address this, we used an enzyme-linked immunosorbent assay to quantify S100A8/A9 heterodimers in bone marrow (BM) plasma from 215 MDS patients and compared S100A8/A9 levels across patients with various disease risks and genotypes. S100A8/A9 levels correlated with ASXL1 variant allele frequencies significantly. Moreover, mutant ASXL1 with concurrent RUNX1, STAG2, ZRSR2, or EZH2 mutations was associated with higher S100A8/A9 levels. We further showed that higher S100A8/A9 independently predicted inferior leukemia-free survival and overall survival in MDS patients, irrespective of age, Revised International Prognostic Scoring System subgroups, and known detrimental mutations. Lastly, through deep-sequenced transcriptomic analysis, we demonstrated that higher S100A8/A9 in the BM intimated a perturbed microenvironment with enhanced myeloid-derived suppressor cell-mediated tumor immune escape signal, altered metabolism, and impairment in the functions and quantities of CD8+ T cells and NK cells. S100A8/A9 in the BM microenvironment may be a potential biomarker in the prognostication of MDS and target for novel therapy.
Description
Date
2023
Publisher
Collections
Files
Keywords
Type
Article
Citation
Wang YH, Lin CC, Yao CY, Amaral F, Yu SC, Kao CJ, et al. High BM plasma S100A8/A9 is associated with a perturbed microenvironment and poor prognosis in myelodysplastic syndromes. Blood advances. 2023 Jan 27. PubMed PMID: 36705979. Epub 2023/01/28. eng.