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.read more
Citations
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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.
Journal ArticleDOI
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
Harish Kumar,Suman Mazumder,Neeraj Sharma,Sayak Chakravarti,Mark D. Long,Nathalie Meurice,Joachim L. Petit,Song Liu,Marta Chesi,Sabyasachi Sanyal,A. Keith Stewart,Shaji Kumar,P. Leif Bergsagel,S. Vincent Rajkumar,Linda B. Baughn,Brian G Van Ness,Amit Kumar Mitra +16 more
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
Shuxin Huang,Yujie Zhao,Pengjun Liao,Jinghua Wang,Zhiyang Li,Jiaxiong Tan,Xianfeng Zha,Shaohua Chen,Yangqiu Li,Liye Zhong +9 more
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
Noopur Raje,Kenneth C. Anderson +1 more
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
Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group
Antonio Palumbo,Hervé Avet-Loiseau,Stefania Oliva,Henk M. Lokhorst,Hartmut Goldschmidt,Laura Rosiñol,Paul G. Richardson,S. Caltagirone,Juan J. Lahuerta,Thierry Facon,Sara Bringhen,Michel Attal,Roberto Passera,Andrew Spencer,Massimo Offidani,Shantanu Kumar,Pellegrino Musto,Sagar Lonial,Maria Teresa Petrucci,Robert Z. Orlowski,Elena Zamagni,Gareth J. Morgan,Maletios A. Dimopoulos,Brian G.M. Durie,Kenneth C. Anderson,Pieter Sonneveld,Jesús F. San Miguel,Michele Cavo,S. Vincent Rajkumar,Philippe Moreau +29 more
TL;DR: The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Journal ArticleDOI
Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy
Jens G. Lohr,Petar Stojanov,Scott L. Carter,Peter Cruz-Gordillo,Michael S. Lawrence,Daniel Auclair,Carrie Sougnez,Birgit Knoechel,Joshua Gould,Gordon Saksena,Kristian Cibulskis,Aaron McKenna,Michael A Chapman,Ravid Straussman,Joan Levy,Louise M. Perkins,Jonathan J Keats,Steven E. Schumacher,Mara Rosenberg,Gad Getz,Todd R. Golub +20 more
TL;DR: This article performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity.
Journal ArticleDOI
Heterogeneity of genomic evolution and mutational profiles in multiple myeloma
Niccolo Bolli,Hervé Avet-Loiseau,David C. Wedge,Peter Van Loo,Ludmil B. Alexandrov,Inigo Martincorena,Kevin J. Dawson,Francesco Iorio,Serena Nik-Zainal,Graham R. Bignell,Jonathan Hinton,Yang Li,Jose M. C. Tubio,Stuart McLaren,Sarah O' Meara,Adam Butler,Jon W. Teague,Laura Mudie,Elizabeth Anderson,Naim U. Rashid,Yu-Tzu Tai,Masood A. Shammas,Adam S. Sperling,Mariateresa Fulciniti,Paul G. Richardson,Giovanni Parmigiani,Florence Magrangeas,Stephane Minvielle,Philippe Moreau,Michel Attal,Thierry Facon,P. Andrew Futreal,Kenneth C. Anderson,Peter J. Campbell,Nikhil C. Munshi +34 more
TL;DR: The myeloma genome is heterogeneous across the cohort, and exhibits diversity in clonal admixture and in dynamics of evolution, which may impact prognostic stratification, therapeutic approaches and assessment of disease response to treatment.
Journal ArticleDOI
Clinical and biologic implications of recurrent genomic aberrations in myeloma
Rafael Fonseca,Emily A. Blood,Montserrat Rué,David P. Harrington,Martin M. Oken,Robert A. Kyle,Gordon W. Dewald,Brian G Van Ness,Scott Van Wier,Kimberly J. Henderson,Richard J. Bailey,Philip R. Greipp +11 more
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).