RESUMEN
There have been significant recent advances in the understanding of the role of metabolism in normal and malignant B-cell biology. Previous research has focused on the role of MYC and mammalian target of rapamycin (mTOR) and how these interact with B-cell receptor signaling and hypoxia to regulate glycolysis, glutaminolysis, oxidative phosphorylation (OXPHOS) and related metabolic pathways in germinal centers. Many of the commonest forms of lymphoma arise from germinal center B-cells, reflecting the physiological attenuation of normal DNA damage checkpoints to facilitate somatic hypermutation of the immunoglobulin genes. As a result, these lymphomas can inherit the metabolic state of their cell-of-origin. There is increasing interest in the potential of targeting metabolic pathways for anti-cancer therapy. Some metabolic inhibitors such as methotrexate have been used to treat lymphoma for decades, with several new agents being recently licensed such as inhibitors of phosphoinositide-3-kinase. Several other inhibitors are in development including those blocking mTOR, glutaminase, OXPHOS and monocarboxylate transporters. In addition, recent work has highlighted the importance of the interaction between diet and cancer, with particular focus on dietary modifications that restrict carbohydrates and specific amino acids. This article will review the current state of this field and discuss future developments.
RESUMEN
The first cases of coronavirus disease 2019 (COVID-19) were detected in Wuhan, China, in December 2019. Since this time a concerted global effort of research and observational data gathering has meant that a great deal has been learnt about the impact of COVID-19 in patients with lymphoid malignancies. Approximately one-third of patients with lymphoid malignancies who acquire COVID-19 and have it severely enough to require hospital assessment will die from this infection. Major risk factors for a poor outcome are age and co-morbidities, but when these are taken into account lymphoma patients have a slightly greater than 2-fold increased risk compared to the general population. Notably, despite early concerns regarding the particular vulnerability of lymphoma patients due to the immunosuppressive effects of therapy, active treatment, including B-cell depleting agents such as rituximab, do not appear to be associated with an increased risk of a poorer outcome. Indeed, some treatments such as ibrutinib may be beneficial due to their modulation of the potential fatal hyperinflammatory phase of infection. There are risks associated with hemopoietic stem cell transplantation, but the collective experience is that these can be minimized by preventive strategies and that the majority of transplant recipients with COVID-19 infection will survive. Many questions remain including those regarding the outcome of COVID-19 infection in the rarer lymphoid malignancies and the efficacy of COVID-19 vaccines in lymphoma patients. This review aims to discuss these issues and present a summary of the current knowledge of the impact of COVID-19 in lymphoid malignancies.