Ineffective hematopoiesis is the major characteristic of early myelodysplastic syndromes.Its pathophysiology relies on a diversity of mechanisms supported stable by genetic events that develop in aging hematopoietic stem cells.Deletion and mutations trigger epigenetic modifications, and co-transcriptional and post-transcriptional deregulations of gene expression.Epistatic interactions between mutants may aggravate the phenotype.Amplification of minor subclones containing mutations that promote their growth and suppress the others drives the clonal evolution.
Aging also participates in reprogramming the immune microenvironment towards an inflammatory state, which precedes the expansion of immunosuppressive cells such as Tregs and myeloid-derived suppressive cells that Ski de fond - Accessoires - Fixations - Back-country alters the anti-tumor response of effector cells.Integrating biomarkers of transcription/translation deregulation and immune contexture will help the design of personalized treatments.