Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia.
Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia.
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三氧化二砷联合达沙替尼：治疗费城染色体阳性急性淋巴细胞白血病的新策略
DOI：
10.1111/jcmm.13436
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Mi J
中科院分区：
文献类型：
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作者：
Wang T;Cheng C;Peng L;Gao M;Xi M;Rousseaux S;Khochbin S;Wang J;Mi J
酪氨酸激酶抑制剂（TKI）显著改善了费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）的预后，Ph+ ALL是最常见和最具侵袭性的血液恶性肿瘤之一。然而，TKI耐药性仍然是一个未解决的问题。在本研究中，我们研究了添加三氧化二砷（ATO）对达沙替尼（第二代TKI）治疗Ph+ ALL的作用的影响。我们发现ATO与达沙替尼在TKI敏感和耐药Ph+ ALL细胞系中协同作用，增加细胞凋亡，并揭示了潜在的机制。事实上，ATO和达沙替尼联合使用通过激活UPR凋亡IRE 1/JNK/JNK A轴，同时中和ATO单独激活的UPR ATF 4依赖性抗凋亡轴，导致严重的细胞凋亡。此外，ATO和达沙替尼联合使用抑制了几种基因的表达，我们之前已经证明这与ALL患者的生存概率较短相关。总体而言，这些数据支持ATO联合达沙替尼作为Ph+ ALL患者的新型治疗方案。
Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of Philadelphia chromosome‐positive acute lymphoblastic leukaemia (Ph+ ALL), one of the most common and aggressive forms of haematological malignancies. However, TKI resistance has remained an unsolved issue. In this study, we investigate the impact of adding arsenic trioxide (ATO) on the action of Dasatinib, a second‐generation TKI, in Ph+ ALL. We show that ATO cooperates with Dasatinib in both TKI‐sensitive and resistant Ph+ ALL cell lines to increase apoptosis and we unravel the underlying mechanisms. Indeed, combining ATO and Dasatinib leads to severe cell apoptosis by activating the UPR apoptotic IRE1/JNK/PUMA axis, while neutralizing the UPR ATF4‐dependent anti‐apoptotic axis, activated by ATO alone. Additionally, ATO and Dasatinib in combination repress the expression of several genes, which we previously showed to be associated with shorter survival probability in ALL patients. Overall these data support the use of ATO in combination with Dasatinib as a novel therapeutic regimen for Ph+ ALL patients.
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影响因子：
6.2
作者：
Ravandi F;O'Brien SM;Cortes JE;Thomas DM;Garris R;Faderl S;Burger JA;Rytting ME;Ferrajoli A;Wierda WG;Verstovsek S;Champlin R;Kebriaei P;McCue DA;Huang X;Jabbour E;Garcia-Manero G;Estrov Z;Kantarjian HM
通讯作者：
Kantarjian HM
DOI：
10.1074/jbc.m109.014092
发表时间：
2010-02-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Armstrong JL;Flockhart R;Veal GJ;Lovat PE;Redfern CP
通讯作者：
Redfern CP
影响因子：
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作者：
Wang J;Mi JQ;Debernardi A;Vitte AL;Emadali A;Meyer JA;Charmpi K;Ycart B;Callanan MB;Carroll WL;Khochbin S;Rousseaux S
通讯作者：
Rousseaux S
影响因子：
5.6
作者：
Chen JH;Kuo HC;Lee KF;Tsai TH
通讯作者：
Tsai TH
影响因子：
21.3
作者：
通讯作者：
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