Ubiquitination and DNA Repair in Multiple Myeloma

L. Crawford, A. Irvine
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Abstract

Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal pro- liferation of malignant plasma cells in the bone marrow. MM cells are characterized by genomic abnormalities that arise during the pathogenesis of disease and accumulate during progression. DNA repair pathways are critical to repair the plethora of DNA lesions that occur in MM, and deregulation of these pathways is implicated in disease onset and survival. The ubiquitin proteasome system has emerged as a central player in the regulation of DNA damage response (DDR). In this chapter, we review defects within the ubiquitin proteasome system that are associated with abnormal DNA damage response in MM and discuss current and potential novel ways of targeting these aberra- tions in the clinic.
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多发性骨髓瘤的泛素化和DNA修复
多发性骨髓瘤(MM)是一种以骨髓恶性浆细胞克隆增殖为特征的血液肿瘤。MM细胞的特征是在疾病发病过程中出现的基因组异常,并在进展过程中积累。DNA修复途径对于修复MM中发生的大量DNA损伤至关重要,而这些途径的失调与疾病的发病和生存有关。泛素蛋白酶体系统在DNA损伤反应(DDR)的调控中起着核心作用。在本章中,我们回顾了泛素蛋白酶体系统中与MM异常DNA损伤反应相关的缺陷,并讨论了目前和潜在的临床靶向这些异常的新方法。
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