期刊
BLOOD
卷 123, 期 7, 页码 1040-1050出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-08-522698
关键词
-
类别
资金
- National Institutes of Health (National Cancer Institute) [CA096899, CA034196]
- National Institutes of Health (National Institute of Allergy and Infectious Diseases) [AI04669]
- National Institutes of Health (National Cancer Institute) T32 training grant [CA130807]
- American Cancer Society Postdoctoral Fellowship [125087-PF-13-247-01-LIB]
Although prognosis has improved for children with T-cell acute lymphoblastic leukemia (T-ALL), 20% to 30% of patients undergo induction failure (IF) or relapse. Leukemia-initiating cells (LICs) are hypothesized to be resistant to chemotherapy and to mediate relapse. We and others have shown that Notch1 directly regulates c-Myc, a known regulator of quiescence in stem and progenitor populations, leading us to examine whether c-Myc inhibition results in efficient targeting of T-ALL-initiating cells. We demonstrate that c-Myc suppression by small hairpin RNA or pharmacologic approaches prevents leukemia initiation in mice by eliminating LIC activity. Consistent with its anti-LIC activity in mice, treatment with the BET bromodomain BRD4 inhibitor JQ1 reduces C-MYC expression and inhibits the growth of relapsed and IF pediatric T-ALL samples in vitro. These findings demonstrate a critical role for c-Myc in LIC maintenance and provide evidence that MYC inhibition may be an effective therapy for relapsed/IF T-ALL patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据