Pathogenesis and inflammaging in myelodysplastic syndrome

Area of Science:

• Hematology
• Immunology
• Gerontology

Background:

• Myelodysplastic syndromes (MDS) are age-related clonal hematologic neoplasms.
• Systemic inflammation and disordered signaling are implicated in MDS pathogenesis.
• Inflammaging, a sterile inflammation associated with aging, is increasingly recognized.

Purpose of the Study:

• To review the concepts of inflammaging and MDS pathogenesis.
• To explore the causal relationship between inflammaging and MDS.
• To introduce novel framing mechanisms: 'pre-clonal inflammaging' and 'clonal inflammaging'.

Main Methods:

• Literature review and conceptual synthesis.
• Contextualizing inflammaging and aging hematopoietic system research.
• Connecting current understanding to MDS etiology via clonal hematopoiesis (CHIP).

Main Results:

• MDS pathogenesis is complex, involving genetic and phenotypic diversity.
• Inflammaging's role in myeloid malignancies, particularly MDS arising from CHIP, is under investigation.
• A bidirectional relationship between aging, inflammation, and CHIP is proposed.

Conclusions:

• Inflammaging may play a crucial role in MDS pathogenesis, potentially preceding or coinciding with clonal evolution.
• Novel conceptual frameworks ('pre-clonal inflammaging' and 'clonal inflammaging') offer new perspectives.
• Harmonizing research on aging, inflammation, and MDS is essential for understanding disease etiology.