Promote Arsenic Trioxide Resistance in Chronic Lymphoid Leukemia Through Mitochondria Quality Control.

In clinical practice, arsenic trioxide can be used to treat a subset of R/R CML patients, but resistance tends to reappear quickly. We designed an experiment to study arsenic trioxide resistance in K-562 cells. Previously, we identified the gene as potentially responsible for arsenic trioxide resistance in K-562 cells gene chip screening followed by high-content screening. We aimed to investigate the role and mechanism of the gene in K-562 cells, an arsenic trioxide-resistant chronic myeloid leukemia cell line. lentiviral vector-mediated siRNA transfection was performed on K-562 cells. The roles of in cell proliferation, apoptosis and cell cycle pathways, and colony formation were analyzed by CCK-8 assay, fluorescence-activated cell sorting, and soft agar culture, respectively. Gene chip screening was used to define the possible downstream pathways of . Western blot was performed to further validate the possible genes mediated by for arsenic trioxide resistance in patients with chronic myeloid leukemia. downregulation significantly inhibited growth, promoted apoptosis, decreased colony formation, reduced the duration of the G1 phase, and increased the duration of the S phase of K-562 cells. Western blot results confirmed that may modulate the apoptosis and proliferation of arsenic trioxide-resistant chronic myeloid leukemia cells through the mediation of MAP3K7, CDK4, and PINK1. is a potential therapeutic target for patients with arsenic trioxide-resistant chronic myeloid leukemia.