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Correction of Bcl ‐x splicing improves responses to imatinib in chronic myeloid leukaemia cells and mouse models
Author(s) -
Zhang Jing,
Wang Yan,
Li ShuQi,
Fang Le,
Wang XiaoZhong,
Li Jing,
Zhang HaiBin,
Huang Bo,
Xu YanMei,
Yang WeiMing,
Lin Jin,
Min QingHua,
Liao ZhiHua,
Wu Yan,
Liu Jing
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16472
Subject(s) - rna splicing , cancer research , imatinib mesylate , k562 cells , imatinib , in vivo , myeloid leukemia , medicine , myeloid , biology , leukemia , immunology , gene , genetics , rna
Summary Imatinib mesylate (IM) resistance has become a major clinical problem for chronic myeloid leukaemia (CML). It is known that Bcl‐x splicing is deregulated and is involved in multiple malignant cancer initiation and chemotherapy resistance, including CML. The aim of the present study was to correct the abnormal splicing of Bcl‐x in CML and investigate the subsequent malignant phenotype changes, especially response to IM. The aberrant Bcl‐x splicing in CML cells was effectively restored using vivo‐Morpholino Antisense Oligomer (vMO). CCK‐8 cell viability assay and flow cytometry showed that restoring of Bcl‐x splicing increases IM‐induced growth inhibition and apoptosis of K562 cells. Moreover, a more significant similar phenomenon was observed in imatinib‐resistant CML cell lines K562/G01. Finally, establishment of CML xenograft model had also proved that correcting Bcl‐x splicing in vivo can also enhance the anti‐tumor effect of IM. Our findings suggest that vMO co‐operating with IM can effectively increase the sensitivity of CML cells to IM both in vitro and in vivo , and Bcl‐x splicing could become good candidates for chemotherapy‐sensitized target in IM‐resistant CML.