骨髓瘤硼替佐米耐药相关突变教材教学课件.pptx

MM硼替佐米相关突变;NRAS、KRAS PSMB5 NF-κB通路持续活化相关 HSP:HSP90 HSP27;方法：MassARRAY? DNA质谱阵列基因分析 NRAS-MUT: 1、硼替佐米单药耐药相关 2、PFS时间短 3、不影响硼替佐米联合大剂量DEX方案化疗的患者的预后 ;Interestingly, KRAS but not NRASmutation was significantly associated with TP53 mutation (15% of those with KRAS mutation versus 3% of those without, P = 0.014). when we analyzed the impact of KRAS and NRAS mutations on survival separately, only KRAS and not NRAS mutations were significantly associated with shorter overall survival and progression free survival.;体外实验：we here developed high levels (45- to 129-fold) of acquired resistance to bortezomib in human myelomonocytic THP1 cells by exposure to stepwise increasing (2.5-200 nM) concentrations of bortezomib. an Ala49Thr mutation residing in a highly conserved bortezomib-binding pocket in the PSMB5 protein a dramatic overexpression (up to 60-fold) of PSMB5 protein but not of other proteasome subunits including PSMB6, PSMB7, and PSMA7, high levels of cross-resistance to β5 subunit-targeted cytotoxic peptides 4A6, MG132, MG262, and ALLN, but not to a broad spectrum of chemotherapeutic drugs no marked changes in chymotrypsin-like proteasome activity （类胰凝乳蛋白酶蛋白酶体） restoration of bortezomib sensitivity in bortezomib-resistant cells by siRNA-mediated silencing ofPSMB5 gene expression