Suppression Of Aberrant Activation Of NF-κB Pathway In Drug-resistant Leukemia Stem Cells Contributes To Parthenolide-potentiated Reversal Of Drug Resistance In Leukemia.
Suppression Of Aberrant Activation Of NF-κB Pathway In Drug-resistant Leukemia Stem Cells Contributes To Parthenolide-potentiated Reversal Of Drug Resistance In Leukemia.
复制标题
抑制耐药白血病干细胞中 NF-κB 通路的异常激活有助于小白菊内酯增强白血病耐药性的逆转
DOI：
10.7150/jca.52641
复制
发表时间：
2021
影响因子：
3.9
通讯作者：
Wei HL
中科院分区：
文献类型：
--
作者：
Yi J;Wang L;Wang XY;Sun J;Yin XY;Hou JX;Chen J;Xie B;Wei HL
尽管许多针对白血病干细胞（LSC）特定特征的药物在白血病的临床治疗中具有实质性应用，但LSC复发并导致耐药性白血病。因此，有必要明确LSC在复发性和耐药性白血病中的独特特征，并探索针对这些特征的药物。我们的临床数据表明，与未经治疗的患者相比，复发的急性髓系白血病患者的乳腺癌耐药蛋白（BCRP）和P-糖蛋白（P-gp）表达增强的LSC比例更高。结果表明，与敏感K562细胞来源的LSC相比，耐药K562/ADM细胞来源的LSC具有更高的化疗耐药性，因此我们将这些细胞称为“耐药LSC”。随后，进一步利用基因芯片分析耐药LSCs中NF-κB通路的异常激活。此外，小白菊内酯（PTL）是一种特异性 NF-κB 抑制剂，可有效消除耐药 LSC，并通过下调 NF-κB 通路介导的 P-gp 表达，增强 K562/ADM 细胞对阿霉素诱导的细胞凋亡的敏感性。这些发现使得LSCs的研究领域更加丰富，并为难治性和复发性白血病的治疗提供了潜在的治疗策略。
Although many drugs that targeted the specific features of leukemia stem cells (LSCs) have substantial application in the clinical treatment of leukemia, the LSCs relapsed and caused drug-resistant leukemia. Therefore, it is necessary to identify the unique features of LSCs in relapsing and drug-resistant leukemia and also to explore the drugs that directed at these features. Our clinical data have indicated that relapsed patients with acute myeloid leukemia have more abundant proportion of LSCs with enhanced breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) expression when compared to the untreated patients. The results showed that compared with LSCs derived from sensitive K562 cells, LSCs from drug-resistant K562/ADM cells have much higher chemotherapeutic resistance, and so we termed these cells as “drug-resistant LSCs”. Subsequently, aberrant activation of NF-κB pathway in drug-resistant LSCs was further using gene chip analysis. Also, parthenolide (PTL), which is a specific NF-κB inhibitor, effectively eliminated drug-resistant LSCs and enhanced the sensitivity of K562/ADM cells to doxorubicin-induced apoptosis by down-regulating NF-κB pathway-mediated P-gp expression. These findings make the research area of LSCs more abundant and provide a potential therapeutic strategy for the treatment of refractory and relapsed leukemia.
登录
查看更多内容
影响因子：
3.8
作者：
Kandi V;Kandi S
通讯作者：
Kandi S
影响因子：
23.9
作者：
Lagadinou, Eleni D.;Sach, Alexander;Callahan, Kevin;Rossi, Randall M.;Neering, Sarah J.;Minhajuddin, Mohammad;Ashton, John M.;Pei, Shanshan;Grose, Valerie;O'Dwyer, Kristen M.;Liesveld, Jane L.;Brookes, Paul S.;Becker, Michael W.;Jordan, Craig T.
通讯作者：
Jordan, Craig T.
影响因子：
20.3
作者：
Guzman, ML;Rossi, RM;Jordan, CT
通讯作者：
Jordan, CT
DOI：
10.2174/1386207319666160517115158
发表时间：
2016-01-01
影响因子：
1.8
作者：
Tripathi, Anushree;Misra, Krishna
通讯作者：
Misra, Krishna
影响因子：
20.3
作者：
Graham, SM;Jorgensen, HG;Holyoake, TL
通讯作者：
Holyoake, TL