Int J Med Sci 2016; 13(5):365-373. doi:10.7150/ijms.14989
EphB4/ephrinB2 Contributes to Imatinib Resistance in Chronic Myeloid Leukemia Involved in Cytoskeletal Proteins
1. Department of Hematology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou 510515, Guangdong, China
2. Department of Paediatric Hematology and Oncology, Clinical Center of Tumor Therapy, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510000, China
3. Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University, 1 Tongdao Avenue North, Hohhot 010059, China
* Lin Li and Na Xu contributed equally to this work and should be considered as co-first authors.
Li L, Xu N, Zhang Jf, Xu Ll, Zhou X, Huang Bt, Li Yl, Liu Xl. EphB4/ephrinB2 Contributes to Imatinib Resistance in Chronic Myeloid Leukemia Involved in Cytoskeletal Proteins. Int J Med Sci 2016; 13(5):365-373. doi:10.7150/ijms.14989. Available from http://www.medsci.org/v13p0365.htm
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.
Keywords: Chronic myelogenous leukemia, imatinib, EphB4/ephrin B2, shRNA