Pathogenic and Clinical Implications of the 2-Way Interplay Between Clonal Hematopoiesis of Indeterminate Potential...

Area of Science:

• Hematology
• Oncology
• Immunology

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition increasingly found in multiple myeloma (MM) patients.
• CHIP's role in MM pathogenesis, clinical course, and treatment response is under investigation.
• Phylogenetic analysis shows CHIP and MM do not share a common clonal origin.

Purpose of the Study:

• To review the current evidence on the translational and clinical impact of CHIP in MM.
• To explore the bidirectional interplay between CHIP and MM, particularly concerning the tumor microenvironment (TME) and therapeutic interventions.

Main Methods:

• Review of existing literature, including phylogenetic studies and single-cell RNA sequencing data.
• Analysis of the association between CHIP, MM, and the tumor microenvironment (TME).
• Evaluation of the impact of anti-MM therapies on CHIP clone expansion.

Main Results:

• CHIP does not consistently impact MM survival but is linked to increased treatment-related toxicities.
• CHIP is associated with a more inflammatory and immunosuppressive TME, involving dysfunctional myeloid and T cells.
• Anti-MM therapies like alkylators and immunomodulatory drugs may promote the expansion of pre-existing CHIP clones.

Conclusions:

• CHIP may amplify MM-driven inflammation and therapy-induced inflammation, influencing MM progression and treatment outcomes.
• Therapeutic pressure can alter CHIP clonal architecture, suggesting a dynamic interplay.
• Understanding CHIP dynamics is crucial for optimizing MM treatment strategies, predicting toxicities, and personalizing patient care.