title: Loss of p53 exacerbates multiple myeloma phenotype by facilitating the reprogramming of hematopoietic stem/progenitor cells to malignant plasma cells by MafB.
abstract: Multiple myeloma (MM) is a serious, mostly incurable human cancer of malignant plasma cells. Chromosomal translocations affecting MAFB are present in a significant 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 efficiency of the MafB-induced MM reprogramming of normal HS/P-Cs to terminally differentiated malignant plasma cells is enhanced by p53 deficiency, in analogy to what happens in reprogramming to pluripotency. These results raise caution about interfering with p53 function when treating multiple myeloma.
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Salamanca, Spain. cvd@usal.es
authors.forename: Carolina
authors.initials: C
authors.lastname: Vicente-Dueñas
authors.forename: Inés
authors.initials: I
authors.lastname: González-Herrero
authors.forename: María Begoña
authors.initials: MB
authors.lastname: García Cenador
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: García Criado
authors.forename: Isidro
authors.initials: I
authors.lastname: Sánchez-García
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D057898:Hemizygote; D006720:Homozygote; D006801:Humans; D051258:MafB Transcription Factor / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53