Lymphoid clonal hematopoiesis: implications for malignancy, immunity, and treatment

Area of Science:

• Hematology
• Oncology
• Immunology

Background:

• Clonal hematopoiesis (CH) typically involves mutations linked to myeloid malignancies or mCAs linked to lymphoid malignancies.
• A paradigm shift emerged with the identification of specific mutations and mCAs associated with lymphoid malignancy risk.

Purpose of the Study:

• To define lymphoid clonal hematopoiesis (L-CH) and its origins.
• To review L-CH's role in autoimmunity, immunodeficiency, and therapy-induced conditions.

Main Methods:

• Literature review focusing on recent studies and established knowledge on CH.
• Analysis of genetic alterations (somatic mutations, mCAs) and their association with lymphoid disorders.
• Exploration of L-CH's developmental trajectory from stem cells to differentiated progeny.

Main Results:

• L-CH is characterized by distinct mutations and mCAs that elevate lymphoid malignancy risk.
• L-CH can originate not only from stem cells but also from partially or fully differentiated lymphocyte precursors.
• Evidence suggests L-CH is implicated in late-onset autoimmunity and immunodeficiency.

Conclusions:

• L-CH represents a distinct entity within clonal hematopoiesis, challenging previous associations.
• Understanding L-CH origins and associations is crucial for diagnosing and managing lymphoid malignancies, autoimmunity, and immunodeficiency.
• Therapy-related L-CH following chemotherapy or stem cell transplantation warrants further investigation.