CircBA9.3 supports the survival of leukaemic cells by up-regulating c-ABL1 or BCR-ABL1 protein levels

Blood Cells Mol Dis. 2018 Nov:73:38-44. doi: 10.1016/j.bcmd.2018.09.002. Epub 2018 Sep 14.

Abstract

The unchecked tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. Therefore, this oncogene is a highly important therapeutic target for chronic myelogenous leukaemia (CML). Tyrosine kinase inhibitors (TKIs) are an excellent drug treatment for CML patients. However, there are still some patients who are not responsive to TKIs. We found that a novel circular RNA (circRNA), named circBA9.3, is derived from BCR-ABL1. CircBA9.3 can efficiently promote the proliferation and inhibit apoptosis of cancer cells. In addition, some patients with TKI resistance have elevated circBA9.3 expression, which is positively correlated with the level of BCR-ABL1. Furthermore, circBA9.3 is predominantly located in the cytoplasm and enhances c-ABL1 and BCR-ABL1 oncoprotein expression. Thus, circBA9.3 is a molecule associated with increased tyrosine kinase activity that promotes resistance against TKI therapy. In this study, we provided a new potential target for the treatment of TKI-resistant CML patients.

Keywords: BCR-ABL1; Chronic myelogenous leukaemia; Circular RNA; Drug resistance; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Fusion Proteins, bcr-abl / analysis*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-abl / analysis*
  • RNA / analysis
  • RNA / physiology*
  • RNA, Circular

Substances

  • BCR-ABL1 fusion protein, human
  • Protein Kinase Inhibitors
  • RNA, Circular
  • RNA
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl