ZNF224 is a transcriptional repressor of AXL in chronic myeloid leukemia cells

ZNF224 is a KRAB-zinc finger transcription factor that exerts a key tumor suppressive role in chronic myelogenous leukemia. In this study, we identify the receptor tyrosine kinase Axl as a novel target of ZNF224 transcriptional repression activity. Axl overexpression is found in many types of cancer and is frequently associated with drug resistance. Interestingly, we also found that sensitivity to imatinib can be partly restored in imatinib-resistant chronic myelogenous leukemia cells by ZNF224 overexpression and the resulting suppression of Axl expression. These results, in accordance with our previous findings, support the role of ZNF224 in imatinib responsiveness and shed new insights into potential therapeutic use of ZNF224 in imatinib-resistant chronic myelogenous leukemia. •ZNF224 expression inversely correlates with Axl expression in imatinib-sensitive and imatinib-resistant CML cell lines.•The receptor tyrosine kinase Axl is a novel target of ZNF224 transcriptional repression.•ZNF224 expression contributes to restore imatinib sensitivity of imatinib-resistant CML cells, through the repression of Axl.•ZNF224 could represent a new and promising therapeutic target in CML.