Epigenetic Crosstalk between Malignant Plasma Cells and the Tumour Microenvironment in Multiple Myeloma.

ABSTRACT

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.