Is Myelodysplasia a Consequence of Normal Aging?

Abstract

Purpose of Review To review available data on the relationship of MDS and aging and to address the question if biological changes of (premature) aging are a prerequisite for the development of MDS. Recent Findings Whereas the association of MDS with advanced age and some common biologic features of aging and MDS are well established, additional evidence for both, especially on the role of stem cells, the stem cell niche, and inflammation, has been recently described. Summary Biologically, many but not all drivers of aging also play a role in the development and propagation of MDS and vice versa. As a consequence, aging contributes to the development of MDS which can be seen as an interplay of clonal disease and normal and premature aging. The impact of aging may be different in specific MDS subtypes and risk groups.

Attenuated cell cycle and DNA damage response transcriptome signatures and overrepresented cell adhesion processes imply accelerated progression in patients with lower‐risk myelodysplastic neoplasms

“…In GSEA, no gene set for cycling, metabolism and DDR was significant (FDR < 0.1) in C2 and H datasets (Figure S7B). These data support the hypothesis that features that lead to development (and protect against progression) of LR‐MDS manifest largely as a consequence of intrinsic molecular changes in cells that occur in processes of normal HSC ageing 15,16 . The unavailability of BM CD34+ cells from age‐matched healthy controls for prMDS precluded such comparison, but data from healthy controls and stMDS‐age imply that premalignant expression signatures of prMDS are distinct from normal HSC ageing.…”

“…These data support the hypothesis that features that lead to development (and protect against progression) of LR-MDS manifest largely as a consequence of intrinsic molecular changes in cells that occur in processes of normal HSC ageing. 15,16 The unavailability of BM CD34+ cells from age-matched healthy controls for prMDS precluded such comparison, but data from healthy controls and stMDS-age imply that premalignant expression signatures of prMDS are distinct from normal HSC ageing. prMDS CD34+ cells revealed broadly repressed markers of multiple subcategories of DDR among the top 50 downregulated genes when compared to stMDS (Figure S8, Table S4A).…”

ABIN1 (Q478) is Required to Prevent Hematopoietic Deficiencies through Regulating Type I IFNs Expression

“…Given that myelodysplastic syndrome (MDS) is an age‐related disease, the relationship between different types of MDS and age may vary. [ 37 ] First, we conducted hematopoiesis‐related experimental analysis using Abin Q478H/Q478H mice of different ages. We observed that Abin Q478H/Q478H mice displayed a more pronounced anemia and thrombocytopenia at 10 months of age as compared with 5 months of age (Figure 1a).…”

Shallow whole‐genome sequencing of bone marrow aspirates in myelodysplastic neoplasms: A retrospective comparison with cytogenetics

“…They also carry an increased risk of leukemic transformation. The annual incidence of MDS is about 4/100 000 overall and increases with age to 40/100 000 in patients ≥ 70 years 1,3,4 . MDS is diagnosed based on peripheral blood counts and cytology, morphology and conventional cytogenetic analysis (CCA) of bone marrow (BM).…”