Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Cancer Rep (Hoboken). 2019 Apr;2(2):e1139. doi: 10.1002/cnr2.1139. Epub 2018 Oct 7.
Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a disruption of normal bone marrow function. Leukemias are diverse in type, affected population, prognosis, and treatment regimen, yet a common theme in leukemia is the dysregulated metabolism of leukemic cells and leukemic stem cells with respect to their noncancerous counterparts.
In this review, we highlight current findings that elucidate metabolic traits unique to the four major types of leukemia, which confer carcinogenic survival but can be potentially exploited for therapeutic intervention. These metabolic features can work in conjunction with or be independent of unique aspects of the bone marrow microenvironment that can also influence cell survival and proliferation, thus sustaining carcinogenesis.
Deepening our understanding of the interactions of leukemias with their niche environments in vivo will inform future treatments for leukemia, particularly for those that are refractive to tyrosine kinase inhibitors and other therapeutic mainstays.
造血过程中白细胞的致癌转化导致白血病的发生,白血病的特征是免疫细胞功能不全和正常骨髓功能紊乱。白血病的类型、受影响人群、预后和治疗方案各不相同,但白血病的一个共同主题是白血病细胞和白血病干细胞的代谢失调与其非癌性对应物相比。
在这篇综述中,我们强调了目前阐明的发现,这些发现阐明了四种主要类型白血病特有的代谢特征,这些特征赋予了致癌生存能力,但可以被潜在地利用来进行治疗干预。这些代谢特征可以与骨髓微环境的独特方面协同作用,也可以独立于这些方面,这些独特方面也可以影响细胞的存活和增殖,从而维持癌变。
深入了解白血病与其体内龛位环境的相互作用将为白血病的未来治疗提供信息,特别是对那些对酪氨酸激酶抑制剂和其他治疗支柱药物有抗性的白血病。