RGD Reference Report - CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease. - Rat Genome Database

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CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease.

Authors: Johnson, Sarah K  Stewart, James P  Bam, Rakesh  Qu, Pingping  Barlogie, Bart  van Rhee, Frits  Shaughnessy, John D  Epstein, Joshua  Yaccoby, Shmuel 
Citation: Johnson SK, etal., Blood. 2014 Sep 25;124(13):2051-60. doi: 10.1182/blood-2014-02-555813. Epub 2014 Jul 24.
RGD ID: 329845546
Pubmed: PMID:25061178   (View Abstract at PubMed)
PMCID: PMC4186535   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2014-02-555813   (Journal Full-text)

Secreted protein CCN1, encoded by CYR61, is involved in wound healing, angiogenesis, and osteoblast differentiation. We identified CCN1 as a microenvironmental factor produced by mesenchymal cells and overexpressed in bones of a subset of patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our analysis showed that overexpression of CYR61 was independently associated with superior overall survival of MM patients enrolled in our Total Therapy 3 protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM to progress to overt MM. During remission from MM, high levels of CCN1 were associated with superior progression-free and overall survival and stratified patients with molecularly defined high-risk MM. Recombinant CCN1 directly inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells reduced tumor growth and prevented bone destruction in vivo in severe combined immunodeficiency-hu mice. Signaling through αvβ3 was required for CCN1 prevention of bone disease. CYR61 expression may signify early perturbation of the microenvironment before conversion to overt MM and may be a compensatory mechanism to control MM progression. Therapeutics that upregulate CYR61 should be investigated for treating MM bone disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCN1Humanmultiple myeloma exacerbatesIEP mRNA and protein:increased expression:bone marrow (human)RGD 
Ccn1Ratmultiple myeloma exacerbatesISOCCN1 (Homo sapiens)mRNA and protein:increased expression:bone marrow (human)RGD 
Ccn1Mousemultiple myeloma exacerbatesISOCCN1 (Homo sapiens)mRNA and protein:increased expression:bone marrow (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccn1  (cellular communication network factor 1)

Genes (Mus musculus)
Ccn1  (cellular communication network factor 1)

Genes (Homo sapiens)
CCN1  (cellular communication network factor 1)


Additional Information