MCP: When mitochondria make B cells go bad
B-cell chronic lymphocytic leukemia, or B-CLL, is the most common type of leukemia in adults and primarily affects elderly patients. The disease results from a patient’s bone marrow overproducing immature lymphocytes, a form of white blood cells that fight infections less effectively than their healthy counterparts but survive longer, ultimately overwhelming them and spreading unchecked. Unlike acute leukemia, B-CLL can take several years to cause problems for a patient, but it is less responsive to chemotherapy.

While novel treatments have been developed in recent years, they only target the B cells once they’ve mutated to an immature, cancerous state. To develop treatments for B-CLL that might prevent B cells from becoming cancerous in the first place, researchers led by Christopher Gerner at the University of Vienna and Vienna Metabolomics Center have performed a comprehensive proteomics analysis of B-CLL cells and mature B cells in young and elderly patients. They described their work in a paper in the journal Molecular & Cellular Proteomics.
“It could be nice to not only target the cancer cells, but those cells prone to becoming cancer cells,” Gerner said. “What we actually saw when we compared the young and the elderly donors was a very clear signature of mitochondrial stress and metabolic stress.”
Gerner and colleagues found that B-CLL cells have an increased expression of stem cell-associated molecules and a reduced expression of tumor-suppressing molecules and stress-related serotonin transporters as well as an observed increase in glutamine consumption and beta-oxidation of fatty acid.
This indicated that reactive oxidative species, which are carcinogenic and cause damage to cells, were being upregulated, Gerner said, which would explain why the incidence of mutations that lead to B-CLL increases with age. The researchers hope that the alterations in regulation also may provide a proteomic signature for immunosenescence, the immune system’s natural weakening with age.
Gerner and his fellow researchers plan to continue this research by performing their proteomic analysis on blood samples taken from greater numbers of healthy elderly people and B-CLL patients to ultimatelybe able to test when mitochondria have become predisposed for the disease.
“The pressure on those cells was simply different … and this pressure is something I would like to detect and measure in patients,” Gerner said. “That would be the ultimate aim.”
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles

Training AI to uncover novel antimicrobials
Antibiotic resistance kills millions, but César de la Fuente’s lab is fighting back. By pairing AI with human insight, researchers are uncovering hidden antimicrobial peptides across the tree of life with a 93% success rate against deadly pathogens.

AI-designed biomarker improves malaria diagnostics
Researchers from the University of Melbourne engineered Plasmodium vivax diagnostic protein with enhanced yield and stability while preserving antibody-binding, paving the way for more reliable malaria testing.

Matrix metalloproteinase inhibitor reduces cancer invasion
Scientists at the Mayo Clinic engineered a TIMP-1 protein variant that selectively inhibits MMP-9 and reduces invasion of triple-negative breast cancer cells, offering a promising tool for targeted cancer research.

Antibiotic sensor directly binds drug in resistant bacteria
Researchers at Drexel University uncover how the vancomycin-resistant bacterial sensor binds to the antibiotic, offering insights to guide inhibitor design that restores antibiotic effectiveness against hospital-acquired infections.

ApoA1 reduce atherosclerotic plaques via cell death pathway
Researchers show that ApoA1, a key HDL protein, helps reduce plaque and necrotic core formation in atherosclerosis by modulating Bim-driven macrophage death. The findings reveal new insights into how ApoA1 protects against heart disease.

Omega-3 lowers inflammation, blood pressure in obese adults
A randomized study shows omega-3 supplements reduce proinflammatory chemokines and lower blood pressure in obese adults, furthering the understanding of how to modulate cardiovascular disease risk.