Preclinical evaluation of a regimen combining chidamide and ABT-199 in acute myeloid leukemia.
Preclinical evaluation of a regimen combining chidamide and ABT-199 in acute myeloid leukemia.
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西达本胺联合 ABT-199 治疗急性髓系白血病的临床前评价
DOI：
10.1038/s41419-020-02972-2
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发表时间：
2020-09-18
影响因子：
9
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Chen K;Yang Q;Zha J;Deng M;Zhou Y;Fu G;Bi S;Feng L;Xu-Monette ZY;Chen XL;Fu G;Dai Y;Young KH;Xu B
Acute myeloid leukemia (AML) is a heterogeneous myeloid neoplasm with poor clinical outcome, despite the great progress in treatment in recent years. The selective Bcl-2 inhibitor venetoclax (ABT-199) in combination therapy has been approved for the treatment of newly diagnosed AML patients who are ineligible for intensive chemotherapy, but resistance can be acquired through the upregulation of alternative antiapoptotic proteins. Here, we reported that a newly emerged histone deacetylase inhibitor, chidamide (CS055), at low-cytotoxicity dose enhanced the anti-AML activity of ABT-199, while sparing normal hematopoietic progenitor cells. Moreover, we also found that chidamide showed a superior resensitization effect than romidepsin in potentiation of ABT-199 lethality. Inhibition of multiple HDACs rather than some single component might be required. The combination therapy was also effective in primary AML blasts and stem/progenitor cells regardless of disease status and genetic aberrance, as well as in a patient-derived xenograft model carrying FLT3-ITD mutation. Mechanistically, CS055 promoted leukemia suppression through DNA double-strand break and altered unbalance of anti- and pro-apoptotic proteins (e.g., Mcl-1 and Bcl-xL downregulation, and Bim upregulation). Taken together, these results show the high therapeutic potential of ABT-199/CS055 combination in AML treatment, representing a potent and alternative salvage therapy for the treatment of relapsed and refractory patients with AML.
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DOI：
10.1056/nejmoa1513257
发表时间：
2016-01-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Roberts AW;Davids MS;Pagel JM;Kahl BS;Puvvada SD;Gerecitano JF;Kipps TJ;Anderson MA;Brown JR;Gressick L;Wong S;Dunbar M;Zhu M;Desai MB;Cerri E;Heitner Enschede S;Humerickhouse RA;Wierda WG;Seymour JF
通讯作者：
Seymour JF
罗米地辛治疗复发/难治性外周 T 细胞淋巴瘤：关键研究更新表明持久反应。
影响因子：
28.5
作者：
Coiffier B;Pro B;Prince HM;Foss F;Sokol L;Greenwood M;Caballero D;Morschhauser F;Wilhelm M;Pinter-Brown L;Padmanabhan Iyer S;Shustov A;Nielsen T;Nichols J;Wolfson J;Balser B;Horwitz S
通讯作者：
Horwitz S
影响因子：
28.2
作者：
Pan R;Hogdal LJ;Benito JM;Bucci D;Han L;Borthakur G;Cortes J;DeAngelo DJ;Debose L;Mu H;Döhner H;Gaidzik VI;Galinsky I;Golfman LS;Haferlach T;Harutyunyan KG;Hu J;Leverson JD;Marcucci G;Müschen M;Newman R;Park E;Ruvolo PP;Ruvolo V;Ryan J;Schindela S;Zweidler-McKay P;Stone RM;Kantarjian H;Andreeff M;Konopleva M;Letai AG
通讯作者：
Letai AG
释放的 Bim 与 Mcl-1 的结合是 ABT-199 内在耐药性的机制，可通过与 AML 细胞中的柔红霉素或阿糖胞苷组合来克服
DOI：
10.1158/1078-0432.ccr-15-3057
发表时间：
2016-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Niu X;Zhao J;Ma J;Xie C;Edwards H;Wang G;Caldwell JT;Xiang S;Zhang X;Chu R;Wang ZJ;Lin H;Taub JW;Ge Y
通讯作者：
Ge Y
影响因子：
51.1
作者：
DiNardo, Courtney L.;Pratz, Keith W.;Pollyea, Daniel A.
通讯作者：
Pollyea, Daniel A.