ONCOmmunity

Chronic Lymphocytic Leukemia-Derived Exosomes Stimulate Cells From The Microenvironment

Paggetti J, Berchem GJ, Moussay E et al.

Key Points:

Bone marrow mesenchymal stem cells (MSC) and endothelial cells (EC) may provide anti-apoptic stimuli to CLL cells.
Exosomes (extracellular vesicles) involved in communication between CLL cells and stromal/target cells, which in turn secrete cytokines that promote cell survival.
Finding: exosomes derived from CLL cell lines, primary cells culture supernatants and plasma from CLL patients rapidly enters the target cells (MSC/EC)and transfer proteins and miRNA.
These CLL derived exosomes activate key signaling pathways (PI3K, AKT, and MAPK, NF-kB).
They also modulate gene expression in MSC/EC.
Some of these genes encodes cytokines BAFF, IL-6, and IL-8), chemokines (CCL2/MCP-1, CCL5/RANTES, and CXCL1), cell adhesion and migration molecules(ICAM-1 and MMP-1).

Implications:

CLL-exosomes contain pro-oncogenic molecules and strongly affect MSC and EC, causing release of cytokines/chemokines and other oncogenic factors favoring leukemia cell survival and proliferation.