Journal ArticleDOI
Evolutionary biology of high-risk multiple myeloma
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TLDR
This Review discusses end-stage high-risk disease states and how new information is improving the understanding of their evolutionary trajectories, how they may be diagnosed and the biological behaviour that must be addressed if they are to be treated effectively.Abstract:
The outcomes for the majority of patients with myeloma have improved over recent decades, driven by treatment advances. However, there is a subset of patients considered to have high-risk disease who have not benefited. Understanding how high-risk disease evolves from more therapeutically tractable stages is crucial if we are to improve outcomes. This can be accomplished by identifying the genetic mechanisms and mutations driving the transition of a normal plasma cell to one with the features of the following disease stages: monoclonal gammopathy of undetermined significance, smouldering myeloma, myeloma and plasma cell leukaemia. Although myeloma initiating events are clonal, subsequent driver lesions often occur in a subclone of cells, facilitating progression by Darwinian selection processes. Understanding the co-evolution of the clones within their microenvironment will be crucial for therapeutically manipulating the process. The end stage of progression is the generation of a state associated with treatment resistance, increased proliferation, evasion of apoptosis and an ability to grow independently of the bone marrow microenvironment. In this Review, we discuss these end-stage high-risk disease states and how new information is improving our understanding of their evolutionary trajectories, how they may be diagnosed and the biological behaviour that must be addressed if they are to be treated effectively.read more
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The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee.
Elias Campo,Elaine S. Jaffe,James R. Cook,Leticia Quintanilla-Martinez,Steven H. Swerdlow,Kenneth C. Anderson,Pierre Brousset,Lorenzo Cerroni,Laurence de Leval,Stephan Dirnhofer,Ahmet Dogan,Andrew L. Feldman,Falko Fend,Jonathan W. Friedberg,Philippe Gaulard,Paolo Ghia,Steven M. Horwitz,Rebecca L. King,Gilles Salles,Jesús F. San Miguel,John F. Seymour,Steven P. Treon,Julie M. Vose,E. Zucca,Ranjana H. Advani,Stephen M. Ansell,Wing Yan Au,Carlos Barrionuevo,P. Leif Bergsagel,Wing C. Chan,Jeffrey I. Cohen,Andrew Davies,Brunangelo Falini,Irene M. Ghobrial,John R. Goodlad,John G. Gribben,Eric D. Hsi,Brad S. Kahl,Won Seog Kim,Shaji Kumar,Ann S. LaCasce,Camille Laurent,Georg Lenz,John J. Leonard,Michael P. Link,Armando López-Guillermo,Maria-Victoria Mateos,Elizabeth Macintyre,Ari Melnick,Franck Morschhauser,Shigeo Nakamura,Marina Narbaitz,Astrid Pavlovsky,Stefano Pileri,Miguel A. Piris,Barbara Pro,S. Vincent Rajkumar,Steve Rozen,Birgit Sander,Laurie H. Sehn,Margaret A. Shipp,Sonali M. Smith,Louis M. Staudt,Catherine Thieblemont,Thomas Tousseyn,Wyndham H. Wilson,Tadashi Yoshino,Pier Luigi Zinzani,Martin Dreyling,David Scott,Jane N. Winter,Andrew D. Zelenetz +71 more
TL;DR: The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined and some categories considered provisional are now upgraded to definite entities in the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
Journal ArticleDOI
Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial.
Graham H. Jackson,Faith E. Davies,Charlotte Pawlyn,Charlotte Pawlyn,David A Cairns,Alina Striha,Corinne Collett,Anna Hockaday,John R Jones,John R Jones,Bhuvan Kishore,Mamta Garg,Cathy D. Williams,Kamaraj Karunanithi,Jindriska Lindsay,Matthew W Jenner,Gordon Cook,Nigel H. Russell,Martin Kaiser,Martin Kaiser,Mark T. Drayson,Roger G. Owen,Walter M Gregory,Gareth J. Morgan +23 more
TL;DR: Progression-free survival was improved with lenalidomide compared with observation in patients with newly diagnosed multiple myeloma, including cytogenetic risk and transplantation status subgroup analyses.
Journal ArticleDOI
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma
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TL;DR: This work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients, and identifies extensive subclonal structures for 10 of 29 individuals with multiple myeloma.
Journal ArticleDOI
Toward personalized treatment in multiple myeloma based on molecular characteristics.
Charlotte Pawlyn,Faith E. Davies +1 more
TL;DR: It is argued that in order to continue to improve multiple myeloma patient outcomes incorporating such biomarkers into the routine diagnostic workup of patients will allow for the use of personalized, biologically based treatments.
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TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
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TL;DR: It is demonstrated that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival, and a large majority of SCNAs identified in individual cancer types are present in several cancer types.
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