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Multiple Myeloma: Heterogeneous in Every Way

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TLDR
In this article, the authors used single-cell analysis to predict patient prognosis and response to treatment for multiple myeloma (MM) in the bone marrow using a combination of cytogenetics and minimal residual disease.
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.

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Citations
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Journal ArticleDOI

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

TL;DR: Findings indicate that amino acid metabolism disorders are involved in MM, and the potential utility of key amino acid metabolites as diagnostic biomarkers of MM is revealed.
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Epigenetic Crosstalk between Malignant Plasma Cells and the Tumour Microenvironment in Multiple Myeloma

TL;DR: This review discusses the crosstalk between the tumour microenvironment’s epigenetic mechanisms, the progression of multiple myeloma, and the onset of multipleMyeloma complications, such as bone disease.
Journal ArticleDOI

What’s Old is New: The Past, Present and Future Role of Thalidomide in the Modern-Day Management of Multiple Myeloma

TL;DR: Thalidomide-based regimens remain important alternatives for heavily pretreated patients, especially for those who have no access to novel therapies and/or are not eligible for their use (due to renal failure, high-grade myelosuppression, or significant comorbidities).
Journal ArticleDOI

Single-Cell Proteomics and Tumor RNAseq Identify Novel Pathways Associated With Clofazimine Sensitivity in PI- and IMiD- Resistant Myeloma, and Putative Stem-Like Cells

TL;DR: Novel pathways associated with CLF efficacy are identified, including induction of ER stress, autophagy, mitochondrial dysfunction, oxidative phosphorylation, enhancement of downstream cascade of p65-NFkB-IRF4-Myc downregulation, and ROS-dependent apoptotic cell death in myeloma.
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Different expression patterns of VISTA concurrent with PD-1, Tim-3, and TIGIT on T cell subsets in peripheral blood and bone marrow from patients with multiple myeloma

TL;DR: Wang et al. as discussed by the authors found a significant increased percentage of VISTA co-expression with PD-1, Tim-3, and TIGIT in CD3+, CD4+, CD8+, and Treg cells in patients with multiple myeloma.
References
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Journal ArticleDOI

Multiple myeloma

TL;DR: The use of bisphosphonates in patients with multiple myeloma (MM) has clearly demonstrated benefit and reduced morbidity associated with bone disease, but all patients with MM ultimately relapse and succumb to their disease.
Journal ArticleDOI

Clinical and biologic implications of recurrent genomic aberrations in myeloma

TL;DR: A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and - 17p13), intermediate prognosis (- 13q14), and good prognosis groups (all others).
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