EphB4-VAV1 signaling pathway is associated with imatinib resistance in chronic myeloid leukemia cells.
Imatinib (IM) resistant Chronic Myeloid Leukemia (CML) is an important issue to be addressed while treating CML patients. The present study analyzes the role of EphB4-VAV1 signaling in IM-resistant CML. EphB4 and VAV1 were overexpressed in IM-resistant CML patients and K562-R cell line (K562-R). Then, we established stable under-expressing EphB4 cell line K562-R-EphB4-sh. VAV1 was down-regulated in K562-R-EphB4-sh cells. K562-R-EphB4-sh cells gained re-sensitivity to IM and K562-R cells showed mild IM resistance. However, EphB4 was no changed when the VAV1 was down-regulated. EphB4 and VAV1 were overexpressed in IM-resistant CML, VAV1might be the downstream moleculars of EphB4. These results suggest a potential role of EphB4-VAV1 signaling as therapeutic target of IM-resistant CML.
Department of paediatric Hematology and Oncology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Jin-Fang
JF
Zhang
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Na
N
Xu
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Qing-Feng
QF
Du
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Rong
R
Li
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: 602538200@qq.com.
Xiao-Li
XL
Liu
D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D036224:Receptor, EphB4 / Q000378:metabolism*; D015398:Signal Transduction
D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; D000068877:Imatinib Mesylate; D036224:Receptor, EphB4
Chronic myeloid leukemia; EphB4; Imatinib resistance; VAV1