Authors: Carolina Vicente-Dueñas, Inés González-Herrero, María Begoña García Cenador, Francisco Javier García Criado and Isidro Sánchez-García

Carolina Vicente-Dueñas

Corresponding author: cvd@usal.es
Experimental Therapeutics and Translational Oncology Program; Instituto de Biología Molecular y Celular del Cáncer; CSIC/Universidad de Salamanca; Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL); Salamanca, Spain

Inés González-Herrero

Experimental Therapeutics and Translational Oncology Program; Instituto de Biología Molecular y Celular del Cáncer; CSIC/Universidad de Salamanca; Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL); Salamanca, Spain

María Begoña García Cenador

Institute of Biomedical Research of Salamanca (IBSAL); Salamanca, Spain; Departamento de Cirugía; Universidad de Salamanca; Salamanca, Spain

Francisco Javier García Criado

Institute of Biomedical Research of Salamanca (IBSAL); Salamanca, Spain; Departamento de Cirugía; Universidad de Salamanca; Salamanca, Spain

Isidro Sánchez-García

Corresponding author: isg@usal.es
Experimental Therapeutics and Translational Oncology Program; Instituto de Biología Molecular y Celular del Cáncer; CSIC/Universidad de Salamanca; Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL); Salamanca, Spain

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.

Received: September 6, 2012; Accepted: September 11, 2012; Published Online: September 14, 2012

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