Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Chicago, Chicago, IL, USA.
Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Chicago, IL, USA.
Adv Exp Med Biol. 2019;1143:95-128. doi: 10.1007/978-981-13-7342-8_5.
Despite the significant progress that has been made in understanding the biology of leukemia stem cells (LSCs), some key questions regarding the concept of LSCs have not as yet been satisfactorily addressed experimentally. As a result, the clinical relevance of LSCs remains less than clear due to controversies caused largely by technical limitations in efficiently identifying LSCs. This has impeded our ability to fully address the features of genetic heterogeneity and metabolic/epigenetic plasticity of pre-LSCs and LSCs. With the development and use of humanized immunocompromised mice, we are able to more precisely analyze LSCs for their functions and interaction with the bone marrow niche. In addition, some promising targets in LSCs have recently been identified, including Sonic Hedgehog (SHH) and BCL-2, which are highly expressed in AML cells. It is hopeful that new anti-LSC compounds will be tested fully in clinical trials for their efficacy in treating human leukemias.
尽管在理解白血病干细胞 (LSCs) 的生物学方面已经取得了重大进展，但关于 LSCs 概念的一些关键问题尚未得到实验的充分解决。因此，由于技术限制在有效识别 LSCs 方面存在很大的争议，LSCs 的临床相关性仍然不太清楚。这阻碍了我们全面了解前 LSCs 和 LSCs 的遗传异质性和代谢/表观遗传可塑性的能力。随着人源化免疫缺陷小鼠的发展和应用，我们能够更精确地分析 LSCs 的功能及其与骨髓龛的相互作用。此外，最近已经确定了 LSCs 中的一些有前途的靶点，包括在 AML 细胞中高表达的 Sonic Hedgehog (SHH) 和 BCL-2。希望新的抗 LSC 化合物将在临床试验中充分测试其治疗人类白血病的疗效。
