Correction of Bcl‐x splicing improves responses to imatinib in chronic myeloid leukaemia cells and mouse models
- 19 March 2020
- journal article
- research article
- Published by Wiley in British Journal of Haematology
- Vol. 189 (6), 1141-1150
- https://doi.org/10.1111/bjh.16472
Abstract
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.Funding Information
- National Natural Science Foundation of China (81560033, 81660029, 81860034)
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