A new study finds evidence that a genetic enzyme deficiency that affects the ability of cells to produce energy may be behind an often-fatal blood cancer called diffuse large B-cell lymphoma.
Lymphomas arise when a type of white blood cell called lymphocytes grow and multiply uncontrollably. These travel to many parts of the body and form tumors. There are two types of lymphocytes – B-lymphocytes (B-cells) and T-lymphocytes (T-cells).
There are two main types of lymphoma – Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) – an aggressive (fast-growing) lymphoma – is the most common type of NHL: it accounts for up to 30% of new diagnoses in the US.
The new study – published in Nature Communications – concerns diffuse large B-cell lymphoma. There, an international team, including members from the School of Medicine at the University of Texas Health Science Center at San Antonio (UTHSCSA), describes how they found evidence linking disrupted metabolism in cells to the aggressive blood cancer.
In order to function correctly, cells carefully fine tune their metabolism – a complex cluster of chemical reactions that converts food into energy. These chemical reactions are regulated by enzymes, whose activity produces critical metabolites.
Cells keep a close check on their levels of critical metabolites to ensure they have enough energy. For instance, when they are short of glucose, they can synthesize it from other materials – cells are expert recyclers.
Senior author Ricardo C.T. Aguiar, associate professor of hematology-oncology at UTHSCSA, explains that scientists have long believed metabolism is tied to cancer – probably via genetic mutations in metabolic enzymes – but evidence of direct links is scarce, and adds:
“We have discovered a metabolic imbalance that is oncogenic or pro-cancer.”
In their paper, Prof. Aguiar and colleagues describe how they found the gene that codes for an enzyme that is important for cell metabolism is mutated in diffuse large B-cell lymphomas.
Lymphomas containing mutant forms of the gene – called D2HGDH – appear to have too-low levels of a metabolite known as alpha-ketoglutarate (alpha-KG). Cells need steady levels of alpha-KG to remain healthy, as Prof. Aguiar explains:
“When the levels of alpha KG are abnormally low, another class of enzymes called dioxygenases don’t function properly, resulting in a host of additional disturbances.”
He also notes that recent studies have found alpha-KG plays an important role in aging and keeping stem cells healthy, and concludes:
“Thus, the implications of our findings are broad and not limited to cancer biology.”
Grants and support for the study came from various sources, including the Cancer Prevention & Research Institute of Texas, the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health.
Meanwhile, Medical News Today recently learned of a European Journal of Immunology study that showed how the immune system’s natural killer cells lose their killer instinct when they are in the vicinity of lymphoma tumors. Researchers from the Helmholtz Zentrum München, in Germany, suggest much needed new therapies for lymphoma may come from finding ways to restore the power of these cells, which normally help the body fight cancer.