Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells.

ABSTRACT: Tumor relapse and drug resistance are major factors that limit the curability of multiple myeloma (MM). New regimens have improved overall MM survival rates, but patients with high-risk features continue to have inferior outcomes. Chromosome 17p13 deletion (del17p) that includes the loss of the TP53 gene is a high-risk cytogenetic abnormality and is associated with poor clinical outcomes owing to relatively short remissions and the development of pan-drug resistant disease. Increased relapse rates suggest that del17p enhances clonogenic growth, and we found that the loss of p53 increased both the frequency and drug resistance of tumor-initiating MM cells (TICs). Subsequent RNA sequencing (RNA-seq) studies demonstrated significant activation of the Notch signaling pathway and upregulation o

SUBMITTER: Chang YT 

PROVIDER: S-EPMC10368840 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature