Multiple Myeloma: Heterogeneous in Every Way

Abstract

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of tumor plasma cells (PCs) in the bone marrow (BM). Despite considerable advances in terms of treatment, patients’ prognosis is still very heterogeneous. Cytogenetics and minimal residual disease both have a major impact on prognosis. However, they do not explain all the heterogeneity seen in the outcomes. Their limitations are the result of the emergence of minor subclones missed at diagnosis, detected by sensible methods such as single-cell analysis, but also the non-exploration in the routine practice of the spatial heterogeneity between different clones according to the focal lesions. Moreover, biochemical parameters and cytogenetics do not reflect the whole complexity of MM. Gene expression is influenced by a tight collaboration between cytogenetic events and epigenetic regulation. The microenvironment also has an important impact on the development and the progression of the disease. Some of these determinants have been described as independent prognostic factors and could be used to more accurately predict patient prognosis and response to treatment.

Race for the Cure: From the Oldest to the Newest Monoclonal Antibodies for Multiple Myeloma Treatment

“…MM is a very complex disease characterized by sophisticated biogenetic mechanisms regulating the competition between different sub-clones and their evolution in space and in time [ 117 ]. This molecular heterogeneity is responsible for the great variety of clinical manifestations and for the discrepancies among outcomes.…”

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

“…Cancer cells do not proliferate when separated from their surroundings, but they significantly institute solid links with the microenvironment essential for cancer advancement [ 31 , 32 ]. In contrast to solid tumours, where the positions of primary disease and secondary metastases are characteristically different, in MM, we have wide tumour diffusion in multiple places within the BM.…”

Nontargeted and targeted metabolomics approaches reveal the key amino acid alterations involved in multiple myeloma

“…According to these clinical trials ( Fayers et al, 2011 ; Gay et al, 2011 ; Mateos, 2010 ), the combination of diverse drugs, such as proteasome inhibitors, immune-modulatory drugs, monoclonal antibodies, HDAC inhibitors and individual CAR-T cell therapy, and autologous hemopoietic stem cell transplantation with traditional drugs, such as corticosteroids, alkylating agents and anthracyclines, has achieved significant clinical effects, but MM remains an incurable disease. Despite considerable advances in treatment, the prognosis of MM is still very heterogeneous ( Schavgoulidze et al, 2021 ). Several reports have demonstrated the links between MM treatment and its early diagnosis ( Korde et al, 2015 ; Mateos et al, 2013 ).…”