Aasebø Elise, Bartaula-Brevik Sushma, Hernandez-Valladares Maria, Bruserud Øystein
a Section for Hematology, Department of Clinical Science , University of Bergen , Bergen , Norway.
b Proteomics Unit (PROBE), Department of Biomedicine , University of Bergen , Bergen , Norway.
Expert Rev Hematol. 2018 Jan;11(1):13-24. doi: 10.1080/17474086.2018.1407239. Epub 2017 Nov 23.
V-ATPase is a proton pump expressed both in the membrane of intracellular organelles (e.g. endosomes, lysosomes, Golgi structures) and the plasma membrane. It is an important regulator of organellar functions, intracellular molecular trafficking, intercellular communication and intracellular signaling. It is therefore considered as a possible therapeutic target in the treatment of human malignancies. Areas covered: Relevant publications were identified through literature searches in the PubMed database. We searched for original articles and reviews describing the possible importance of V-ATPase for leukemogenesis and chemosensitivity in human myeloid cells, especially acute myeloid leukemia (AML) cells. Expert commentary: The expression of V-ATPase in the primary human AML cells varies between patients, and high levels are associated with high constitutive release of a wide range of soluble mediators. Several of the molecules included in the V-ATPase interactome may also be important in leukemogenesis and/or development of chemoresistance in human AML. Therapeutic targeting of V-ATPase should therefore be regarded as a possible therapeutic strategy in human AML, but the efficiency of such targeting will probably differ between patients. The possibility of toxicity, especially hematological toxicity and immunosuppression, also has to be clarified.
V-ATP酶是一种质子泵，存在于细胞内细胞器（如内体、溶酶体、高尔基体结构）膜和质膜中。它是细胞器功能、细胞内分子运输、细胞间通讯和细胞内信号传导的重要调节因子。因此，它被认为是治疗人类恶性肿瘤的一个可能的治疗靶点。涵盖领域：通过在PubMed数据库中进行文献检索确定了相关出版物。我们搜索了描述V-ATP酶对人类髓系细胞，尤其是急性髓系白血病（AML）细胞白血病发生和化疗敏感性可能重要性的原始文章和综述。专家评论：V-ATP酶在原发性人类AML细胞中的表达在患者之间存在差异，高水平与多种可溶性介质的高组成性释放相关。V-ATP酶相互作用组中包含的几种分子在人类AML的白血病发生和/或化疗耐药性发展中也可能很重要。因此，V-ATP酶的治疗靶向应被视为人类AML的一种可能的治疗策略，但这种靶向的效率可能因患者而异。毒性的可能性，尤其是血液学毒性和免疫抑制，也必须加以阐明。
