Blood: miR-185/PAK6 axis regulates the survival of CML drug-resistant leukemia stem cells, predicting therapeutic reactive

Overcoming drug resistance and targeting cancer stem cells remains a challenge in cancer treatmentTo study the role of miRNAs in regulating drug resistance and the fate of leukemia stem cells (LSCs), the researchers conducted a full transcription group analysis of stem cells/progenitor cells of untreated chronic myeloid leukemia (CML) and found that miR-185 levels could predict The response of CML to ABL tyrosine kinase inhibitors (TKIs)miR-185 has a cancer-suppressing effect, in vitro, restoring their expression can impair the viability of drug-resistant cells, making them sensitive to TKIs, and significantly eliminating lSCs for long-term reproliferation and cell immersion, and exhibiting survival advantages in preclinical xenotransplant modelscombined with mRNA spectral analysis found that PAK6 is a key target of miR-185, pharmacological inhibition of PAK6 can disrupt the RAS/MAPK pathway and mitochondrial activity, making the treatment of drug-resistant cells sensitive to TKIs, miR-185 is a potential predictable biomarker, and dual-targeted miR85-mediated PAK6 activity and BCR-ABL may provide a valuable strategy for overcoming patient resistance