Loss of P53 Exacerbates Multiple Myeloma Phenotype by Facilitating the Reprogramming of Hematopoietic Stem/progenitor Cells to Malignant Plasma Cells by MafB

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2012 Sep 18

PMID 22983007

Citations 16

Authors

Carolina Vicente-Duenas

Ines Gonzalez-Herrero

Maria Begona Garcia Cenador

Francisco Javier Garcia Criado

Isidro Sanchez-Garcia

Affiliations

Soon will be listed here.

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.

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