Platelet-derived microparticles provoke chronic lymphocytic leukemia malignancy through metabolic reprogramming

Area of Science:

• Oncology
• Hematology
• Cell Biology

Background:

• Platelets and inflammation are known drivers of cancer malignancy.
• Platelet-derived microparticles (PMPs) transfer biological cargo, including functional mitochondria, to cancer cells.
• Mitochondrial transfer impacts cancer hallmarks like growth, apoptosis inhibition, and drug resistance, particularly in chronic lymphocytic leukemia (CLL).

Purpose of the Study:

• To investigate the role of PMPs in modulating the metabolic plasticity of CLL cells.
• To understand how PMP-induced metabolic changes influence cancer cell phenotype and disease progression.

Main Methods:

• CLL cell lines were incubated with human PMPs to assess proliferation, mitochondrial DNA copy number, oxygen consumption rate (OCR), ATP production, and reactive oxygen species (ROS) content.
• Bioinformatics tools identified key metabolic reprogramming genes in early vs. advanced CLL stages, validated in PMP-treated CLLs.
• The impact of metabolic reprogramming on CLL growth, survival, mobility, and invasiveness was tested against Cytarabine, Venetoclax, and Plumbagin.

Main Results:

• PMPs significantly induced tumoral growth and invasiveness in CLLs via mitochondrial internalization and OXPHOS stimulation.
• Observed metabolic shifts in PMP-treated CLLs mirrored those in advanced-stage CLL patients.
• Metabolic rewiring enhanced CLL cell resistance to Cytarabine, Venetoclax, and Plumbagin.

Conclusions:

• PMPs represent a novel platelet-mediated pathway in cancer pathogenesis.
• PMPs play a critical role in CLL metabolic reprogramming, driving disease progression and chemoresistance.