Study Maps How Exosomes Hijack Blood Formation

TOPLINE:

Chronic lymphocytic leukemia (CLL) cell–derived exosomes demonstrated the ability to alter healthy donor cell function and suppress normal blood cell formation. These particles affected monocytes, fibrocytes, and lymphocytes, leading to changes in gene expression and protein levels that may contribute to disease progression.

METHODOLOGY:

• Researchers examined CLL cell–derived exosomes and their effects on healthy donor cells, including monocytes, fibrocytes, and lymphocytes.
• Analysis focused on changes in gene expression and protein levels in target cells after exposure to CLL cell–derived exosomes.
• Investigation included assessment of monocyte CD14 and CD16 expression; T-cell checkpoint proteins, programmed cell death protein 1 (PD-1) and CD160; and B-cell apoptosis and CD5 expression.
• RNA sequencing and quantitative real-time polymerase chain reaction were utilized to analyze exosome content, particularly focusing on proapoptotic genes and metabolic pathway activators.

TAKEAWAY:

• CLL cell–derived exosomes demonstrated the ability to alter gene and protein expression in healthy donor monocytes, fibrocytes, and lymphocytes while suppressing normal hematopoiesis.
• Exposure to these exosomes led to increased CD14 and CD16 expression in normal monocytes, mimicking accessory cell profiles, while upregulating T-cell checkpoint proteins PD-1 and CD160.
• The exosomes induced apoptosis and CD5 expression in normal B cells, suggesting not all CD19+/CD5+ cells in patients with CLL are clonal.
• Analysis revealed these exosomes contained RNAs associated with proapoptotic genes and those involved in metabolism, proliferation, and constitutive phosphatidylinositol 3-kinase-mechanistic target of rapamycin pathway activation.

IN PRACTICE:

“CLL cell–derived exosomes inhibited hematopoietic progenitor proliferation, hindering the supportive effect of monocyte-derived fibrocytes. Together, our findings suggest that CLL cell–derived exosomes disrupt the immune and hematopoietic systems and contribute to disease progression in patients with CLL,” wrote the authors of the study.

SOURCE:

The study was led by Ivo Veletic and David M. Harris, The University of Texas MD Anderson Cancer Center in Houston. It was published online on April 4 in Leukemia.

LIMITATIONS:

The researchers noted that the study data are only available upon reasonable request to the corresponding authors for those wishing to reproduce or extend the research, which may limit immediate verification of findings.

DISCLOSURES:

The study received support from the CLL Global Research Foundation. Additional funding was provided through the National Cancer Institute and National Institutes of Health, which support MD Anderson’s core facilities.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.