RESUMO
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.
RESUMO
Background: Philadelphia-negative chronic myeloproliferative neoplasms are a group of clonal hematopoietic disorders including polycythemia vera, essential thrombocythemia, and primary myelofi-brosis. These neoplasms are characterized by an increased risk of thrombotic complications. Several studies have highlighted that the study of vessels of the retina offers the opportunity to visualize, in vivo, the damage to microcirculation that is common in various systemic pathologies. Methods: in our study, forty patients underwent an ophthalmological examination, using non-invasive imaging tech-niques, for analyses of their retinal vascularization. The objective was to correlate the findings ob-tained from this study of the retina with different markers of thrombotic risk, to demonstrate the usefulness of studying retinal vessels as a possible new prognostic biomarker of thrombotic risk in patients affected by Philadelphia-negative chronic myeloproliferative neoplasms. Results: retinal imaging demonstrated changes in the microcirculation, with a reduced vascular density of the deep and superficial capillary plexuses with respect to a normal group, and a correlation between retinal changes and blood parameters. Conclusions: additional research will allow us to determine whether retinal changes in individuals with chronic myeloproliferative neoplasms could be predictive of the development of thrombotic events in these subjects.
RESUMO
In multiple myeloma, cells of the bone marrow microenvironment have a relevant responsibility in promoting the growth, survival, and drug resistance of multiple myeloma plasma cells. In addition to the well-recognized role of genetic lesions, microenvironmental cells also present deregulated epigenetic systems. However, the effect of epigenetic changes in reshaping the tumour microenvironment is still not well identified. An assortment of epigenetic regulators, comprising histone methyltransferases, histone acetyltransferases, and lysine demethylases, are altered in bone marrow microenvironmental cells in multiple myeloma subjects participating in disease progression and prognosis. Aberrant epigenetics affect numerous processes correlated with the tumour microenvironment, such as angiogenesis, bone homeostasis, and extracellular matrix remodelling. This review focuses on the interplay between epigenetic alterations of the tumour milieu and neoplastic cells, trying to decipher the crosstalk between these cells. We also evaluate the possibility of intervening specifically in modified signalling or counterbalancing epigenetic mechanisms.
