Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis.

Myeloproliferative neoplasms are clonal hematological neoplasms characterized by excessive proliferation of cells of erythroid, granulocytic, and megakaryocytic lineage. The genetic mechanisms underlying this group of blood diseases are now known, but new perspectives have recently emerged in the field of epigenetics and particularly related to the possible role of DNA methylation in disease development and progression. DNA methylation regulates different cellular processes, such as proliferation, differentiation, and apoptosis. In myeloproliferative neoplasms, a link has been found between abnormal methylation patterns, such as hypermethylation of tumor suppressors or, conversely, oncogenes hypomethylation, with the progression of the disease, spreading important prognostic and therapeutic implications. This review aims to investigate the relationship between methylation alterations and myeloproliferative neoplasms, emphasizing the ways by which epigenetic dysregulation promotes disease biology.