Tackling Imatinib Resistance via Au‐nanoconjugates using A Cml Resistant Cell Line

Abstract

AbstractChronic myeloid leukemia (CML) is a rare malignant proliferative hematopoietic disease due to overexpression of a tyrosine kinase (TK) derived from the breakpoint cluster region (BCR)‐abelson tyrosine‐protein kinase 1 (ABL1) gene fusion. Imatinib (IM), blocks this tyrosine kinase, and is the first line TK inhibitor (TKI) used in CML treatment. In a high percentage of CML patients, a poor response with relapse and disease progression is associated to acquisition of resistance through different mechanisms, including dysregulation of c‐MYC proto‐oncogene. Gold nanoparticles (AuNPs) are shown to allow improved efficacy in gene silencing approaches toward cancer therapy. Herein, the silencing potential of AuNPs functionalized with antisense oligonucleotides selectively targeting the e14a2 BCR‐ABL1 or the c‐MYC, alone and combination is evaluated. It is demonstrated efficient silencing of gene expression that translated to a downregulation of protein levels in IM resistant CML cells (K562‐IM). This combination allowed for increased death of the malignant cells. These Au‐nanoconjugates may be useful to tackle IM‐resistance mechanisms, providing an additional tool for future combinatory schemes to fight CML with imatinib resistance.