Can we selectively target AML stem cells?
Can we selectively target AML stem cells?
复制标题
DOI：
10.1016/j.beha.2019.101100
复制
发表时间：
2019-12-01
影响因子：
2.1
通讯作者：
Jordan, Craig T.
中科院分区：
文献类型：
--
作者：
Jordan, Craig T.
新生的急性髓系白血病(AML)白血病干细胞(LSC)群体独特地依赖于氨基酸代谢来驱动TCA循环和氧化磷酸化。在从头开始的AML LSC群体中，氧化磷酸化可以被选择性地下调，方法是通过用万乃馨抑制BCL2来干扰氨基酸代谢。虽然以维诺为基础的治疗显示出很高的应答率，但并不是所有的患者都能得到缓解。通过分析个别患者的代谢特性，有可能前瞻性地确定最有可能对以万乃馨为基础的治疗有反应的患者。具体地说，似乎对基于万乃馨的治疗有抵抗力的患者能够使用替代代谢途径来驱动氧化磷酸化。
De novo acute myeloid leukemia (AML) leukemia stem cell (LSC) populations are uniquely dependent on amino acid metabolism to drive the TCA cycle and oxidative phosphorylation. Oxidative phosphorylation can be selectively downregulated in de novo AML LSC populations by perturbing amino acid metabolism via BCL2 inhibition with venetoclax. While venetoclax-based therapies have shown high response rates, not all patients achieve remission. It may be possible to prospectively identify the patients who will most likely respond to venetoclax-based treatment by analyzing the metabolic properties of individual patients. Specifically, it appears that patients who are likely to be resistant to venetoclax-based therapy are able to employ alternate metabolic pathways to drive oxidative phosphorylation.