Abstract
Multiple myeloma (MM) is the second most common hematological malignancy and is attributed to monoclonal proliferation of plasma cells in the bone marrow. Cancer cells including myeloma cells deregulate metabolic pathways to ensure proliferation, growth, survival and avoid immune surveillance, with glycolysis and glutaminolysis being the most identified procedures involved. These disorders are considered a hallmark of cancer and the alterations performed ensure that enough energy is available for rapid cell proliferation. An association between metabolic syndrome, inflammatory cytokinesand incidence of MM has been also described, while the use of metformin and statins has been identified as a positive prognostic factor for the disease course. In this review, we aim to present the metabolic disorders that occur in multiple myeloma, the potential defects on the immune system and the potential advantage of targeting the dysregulated pathways in order to enhance antitumor therapeutics.
Highlights
Multiple myeloma (MM) is the second most common hematologic malignancy and is attributed to bone marrow infiltration by monoclonal plasma cells
Metabolic disorders are considered a hallmark of cancer and the changes that occur in metabolic pathways are necessary to ensure that enough energy is available for rapid cell proliferation and tumor growth
Glucose is transported in the cells, transformed into lactate which induces adenosine triphosphate (ATP) production. This is mediated by hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) that are highly expressed in myeloma [28]
Summary
Multiple myeloma (MM) is the second most common hematologic malignancy and is attributed to bone marrow infiltration by monoclonal plasma cells. Metabolic disorders are considered a hallmark of cancer and the changes that occur in metabolic pathways are necessary to ensure that enough energy is available for rapid cell proliferation and tumor growth. In this context, glycolysis and glutaminolysis are the two main metabolic pathways that are deregulated and might be combined with immune system impairment [15,16]. Myeloma cells undergo metabolic changes as rearrangements involving adjustments in glucose, glutamine pentosepentose phosphate, folate such as rearrangements involving adjustments in glucose, glutamine phosphate, pathway and serine. These alterations might be involved in drug in resistance folate pathway andmetabolism.
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