ASXL1 mutation-related clonal hematopoiesis and age-related diseases: clinical evidence and molecular insights

Area of Science:

• Hematology
• Genetics
• Immunology

Background:

• Clonal hematopoiesis (CH) involves age-related expansion of mutated hematopoietic stem cells, frequently in epigenetic regulators like DNMT3A, TET2, and ASXL1.
• CH is increasingly linked to non-malignant, inflammation-associated diseases (e.g., cardiovascular disease, autoimmune disorders) and increased mortality, primarily from cardiovascular causes.
• ASXL1 mutations in CH are associated with poor outcomes and inflammation but are less understood than TET2 or DNMT3A mutations.

Purpose of the Study:

• To review current epidemiological and experimental data on ASXL1-mutated CH.
• To focus on the role of ASXL1-mutated CH in inflammation-associated diseases.
• To highlight the need for further investigation into ASXL1-driven CH and its systemic effects beyond hematological malignancies.

Main Methods:

• Literature review and synthesis of existing epidemiological and experimental studies.
• Analysis of clinical observations and emerging mechanistic data related to ASXL1 mutations in CH.
• Focus on studies linking ASXL1 mutations to inflammation and non-malignant conditions.

Main Results:

• ASXL1 mutations are strongly associated with adverse clinical outcomes and pro-inflammatory signatures in CH.
• Evidence suggests ASXL1 mutations contribute to clonal expansion and systemic inflammation, extending beyond hematological malignancies.
• ASXL1-mutated CH is implicated in various age-related inflammatory conditions, including cardiovascular disease.

Conclusions:

• ASXL1-mutated CH plays a significant role in systemic inflammation and age-related non-malignant diseases.
• The impact of ASXL1-mutated CH on cardiovascular complications and overall mortality warrants further investigation.
• Deeper research into ASXL1-driven CH is essential to understand its full pathological spectrum and therapeutic implications.