Szymczak Donata, Dybko Jarosław, Kuliczkowski Kazimierz
Department of Hematology, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2018 Feb;27(2):271-275. doi: 10.17219/acem/69261.
Hypoxia, understood as low partial oxygen pressure, has become one of the most explored fields in recent years. Cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs) - potent transcription regulators, and their downstream pathways. In general, HIFs modify energy metabolism, inflammation and immune response, enhance cancer invasion, metastasis, resistance to treatment, and relapse. The influence of HIFs on the progression of leukemia is still under investigation in various studies, but in mice and some human models HIFs have been recognized as leukemia immortalizers by promoting leukemic stem cell quiescence and inhibiting their cell cycle. This makes leukemic stem cells resistant to most known treatment approaches. The role of HIFs in solid tumors and leukemia makes them almost ideal targets for an anticancer treatment. Although the first attempts with new molecules are encouraging, there is a need to investigate the ambiguous role of HIFs to develop a modern antileukemic treatment.
低氧（即低氧分压）已成为近年来研究最为深入的领域之一。细胞对低氧的反应由低氧诱导因子（HIFs）介导，HIFs是强大的转录调节因子，以及它们的下游信号通路。一般来说，HIFs会改变能量代谢、炎症和免疫反应，增强癌症的侵袭、转移、治疗抵抗和复发。HIFs对白血病进展的影响在各种研究中仍在探讨，但在小鼠和一些人类模型中，HIFs已被认为是白血病的永生因子，通过促进白血病干细胞的静止并抑制其细胞周期。这使得白血病干细胞对大多数已知的治疗方法产生抗性。HIFs在实体瘤和白血病中的作用使其几乎成为抗癌治疗的理想靶点。尽管使用新分子的首次尝试令人鼓舞，但仍有必要研究HIFs的模糊作用，以开发现代抗白血病治疗方法。
