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dc.contributor.authorPawlyn, C
dc.contributor.authorMorgan, GJ
dc.date.accessioned2018-07-05T11:35:13Z
dc.date.issued2017-08
dc.identifier.citationNature reviews. Cancer, 2017, 17 (9), pp. 543 - 556
dc.identifier.issn1474-175X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1999
dc.identifier.eissn1474-1768
dc.identifier.doi10.1038/nrc.2017.63
dc.description.abstractThe 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.
dc.formatPrint
dc.format.extent543 - 556
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectPlasma Cells
dc.subjectHumans
dc.subjectMultiple Myeloma
dc.subjectCell Transformation, Neoplastic
dc.subjectTranslocation, Genetic
dc.subjectImmunoglobulins
dc.subjectRisk Factors
dc.subjectEvolution, Molecular
dc.subjectDrug Resistance, Neoplasm
dc.subjectMutation
dc.subjectDNA Copy Number Variations
dc.titleEvolutionary biology of high-risk multiple myeloma.
dc.typeJournal Article
rioxxterms.versionofrecord10.1038/nrc.2017.63
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature reviews. Cancer
pubs.issue9
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Myeloma Biology and Therapeutics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Myeloma Biology and Therapeutics
pubs.publication-statusPublished
pubs.volume17
pubs.embargo.termsNot known
icr.researchteamMyeloma Biology and Therapeuticsen_US
dc.contributor.icrauthorPawlyn, Charlotteen


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