Dysregulation of immune cell and cytokine signalling correlates with clinical outcomes in myelodysplastic syndrome (MDS).
Eur J Haematol
; 108(4): 342-353, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-34963023
ABSTRACT
OBJECTIVES:
Myelodysplastic syndromes (MDS) are characterised by ineffective haematopoiesis. Although hypomethylating agents (HMA) have improved survival in higher-risk MDS, most patients eventually succumb to progressive disease. Utilising samples collected prospectively from three MDS clinical trials, we analysed genetic and immunological biomarkers and correlated them with clinical outcomes.METHODS:
A hundred and fifty four samples were analysed from 133 de novo MDS patients for T-cell and myeloid cell immunophenotyping and gene expression analysis. Treatments were with HMA or immunomodulatory drug (IMiD) alone or in combination.RESULTS:
We observed differences in immune cell subsets between lower- and higher-risk IPSS groups with NKT cells, MDSCs, intermediate-proinflammatory and non-classical monocytes being higher in the latter group, while naïve CD4+ T cells were reduced. Intermediate-proinflammatory monocytes were increased in non-responders and those failing to achieve at least a haematological improvement. Proinflammatory NKT cells were increased at diagnosis for patients failing to derive clinical benefit after 12 months of treatment. Gene expression analysis of paired bone marrow (BM) colony-forming units (CFUs) from diagnosis and 4 cycles post-treatment confirmed that genes involved in cytokine signalling were downregulated in C4 normal colonies.CONCLUSIONS:
These findings support the central roles of dysregulation in innate immunity and inflammatory signalling in the pathogenesis of MDS which correlated with clinical outcomes post-treatment.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Síndromes Mielodisplásicos
/
Leucemia Mieloide Aguda
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Idioma:
En
Revista:
Eur J Haematol
Asunto de la revista:
HEMATOLOGIA
Año:
2022
Tipo del documento:
Article