International journal of medical sciences · 2016
EphB4/ephrinB2 Contributes to Imatinib Resistance in Chronic Myeloid Leukemia Involved in Cytoskeletal Proteins.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Lin, Xu Na, Zhang Jin-Fang, Xu Lu-Lu, Zhou Xuan, Huang Bin-Tao, Li Yu-Ling, Liu Xiao-Li
Аннотация
INTRODUCTION: The mechanism of EphB4/ephrinB2 in the resistance of chronic myelogenous leukemia to imatinib keeps unknown.
METHODS: The imatinib resistant chronic myelogenous leukemia cell line-K562-R, was established. EphB4 receptor expression was detected in patients and resistant cells. Cell migration and drug sensitivity were tested in the EphB4 knockdown cells and mouse models.
RESULTS: The EphB4 receptor was over-expressed in blast crisis patients compared to chronic phase patients. The level of EphB4 receptor expression was associated with a complete cytogenetic response within 12 months. Enhanced expression of the EphB4 receptor was detected in the K562-R cells. EphB4 knockdown inhibited cell migration ability and restored sensitivity to imatinib in vitro and in vivo. Restored sensitivity to imatinib was observed in K562-R cells, along with increased levels of phospho-EphB4 and decreased phosphorylation levels of RhoA, Rac1, and Cdc42.
CONCLUSION: Our study illustrates that aberrant activation of EphB4/ephrinB2 may mediate chronic myeloid leukemia resistance involved in cytoskeletal proteins.
METHODS: The imatinib resistant chronic myelogenous leukemia cell line-K562-R, was established. EphB4 receptor expression was detected in patients and resistant cells. Cell migration and drug sensitivity were tested in the EphB4 knockdown cells and mouse models.
RESULTS: The EphB4 receptor was over-expressed in blast crisis patients compared to chronic phase patients. The level of EphB4 receptor expression was associated with a complete cytogenetic response within 12 months. Enhanced expression of the EphB4 receptor was detected in the K562-R cells. EphB4 knockdown inhibited cell migration ability and restored sensitivity to imatinib in vitro and in vivo. Restored sensitivity to imatinib was observed in K562-R cells, along with increased levels of phospho-EphB4 and decreased phosphorylation levels of RhoA, Rac1, and Cdc42.
CONCLUSION: Our study illustrates that aberrant activation of EphB4/ephrinB2 may mediate chronic myeloid leukemia resistance involved in cytoskeletal proteins.
Предметные рубрики MeSH
AnimalsAntineoplastic AgentsCell MovementCytoskeletal ProteinsDrug Resistance, NeoplasmEphrin-B2FemaleHumansImatinib MesylateK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMiceMice, NudePhosphorylationReceptor, EphB4Xenograft Model Antitumor Assayscdc42 GTP-Binding Proteinrac1 GTP-Binding ProteinrhoA GTP-Binding Protein