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Title

Loss of p53 exacerbates multiple myeloma phenotype by facilitating the reprogramming of hematopoietic stem/progenitor cells to malignant plasma cells by MafB

AuthorsVicente-Dueñas, Carolina ; González-Herrero, Inés ; García-Cenador, Begoña; García-Criado, Francisco Javier; Sánchez García, Isidro
KeywordsMouse models
Cancer stem cell
Cancer therapy
Cell reprogramming
Mafb
Stem cells
Multiple myeloma
Oncogenes
Issue Date2012
PublisherLandes Bioscience
CitationCell Cycle 11(20): 3896-3900 (2012)
AbstractMultiple myeloma (MM) is a serious, mostly incurable human cancer of malignant plasma cells. Chromosomal translocations afecting MAFB are present in a signifcant percentage of multiple myeloma patients. Genetically engineered Sca1-MafB mice, in which MafB expression is limited to hematopoietic stem/progenitor cells (HS/p-Cs), display the phenotypic features of MM. Contrary to many other types of cancer, it is not yet known if the p53 gene plays any essential role in the pathogenesis of this disease. Here, we show, taking advantage of the Sca1-MafB MM mouse model, that loss of p53 does not rescue the multiple myeloma disease, but instead accelerates its development and exacerbates the MM phenotype. therefore, the efciency of the MafB-induced MM reprogramming of normal HS/p-Cs to terminally diferentiated malignant plasma cells is enhanced by p53 defciency, in analogy to what happens in reprogramming to pluripotency. these results raise caution about interfering with p53 function when treating multiple myeloma.
URIhttp://hdl.handle.net/10261/134239
DOI10.4161/cc.22186
Identifiersdoi: 10.4161/cc.22186
issn: 1538-4101
e-issn: 1551-4005
Appears in Collections:(IBMCC) Artículos
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