Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment

被引:7
作者
Li, Zheng [1 ,2 ]
Wang, Jun [1 ,2 ]
Ge, Shuai-Shuai [1 ,2 ]
Qiu, Qiao-Cheng [1 ,2 ]
Du, Jia-Hui [3 ]
Shan, Shuang-Shuang [3 ]
Shen, Xiang-Dong [1 ,2 ]
Wan, Chao-Ling [1 ,2 ]
Wang, Bin-Ru [1 ,2 ]
Wu, De-Pei [1 ,2 ]
Qiu, Hui-Ying [1 ,2 ]
Xue, Sheng-Li [1 ,2 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Natl Clin Res Ctr Hematol Dis, Suzhou, Peoples R China
[2] Soochow Univ, Collaborat Innovat Ctr Hematol, Inst Blood & Marrow Transplantat, Suzhou, Peoples R China
[3] Suzhou Vocat Hlth Coll, Suzhou Key Lab Med Biotechnol, Suzhou, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2022年 / 12卷
基金
中国国家自然科学基金;
关键词
venetoclax; azacitidine; midostaurin; t(8; 21); relapsed acute myeloid leukemia; KIT mutation; targeted therapy; MUTATIONS; CANCER; ADULTS;
D O I
10.3389/fonc.2022.841276
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations.
引用
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页数:6
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