CBR1 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the CBR1 gene in the human K-562 cell line. This product provides a heterogeneous pool of K-562 cells with targeted disruption of CBR1, generated by CRISPR/Cas9-mediated gene editing. The polyclonal nature offers a diverse loss-of-function model that captures a range of genetic backgrounds arising from gene disruption, suitable for studying CBR1-dependent processes without the biases of single-cell clonal expansion. Researchers can employ this knockout population to dissect the role of CBR1 in carbonyl metabolism, oxidative stress response, and drug sensitivity within a leukemia context.
The host K-562 cell line is a lymphoblastoid cell line established from the pleural effusion of a 53-year-old female with chronic myeloid leukemia in blast crisis. K-562 cells are Philadelphia chromosome positive and express the BCR-ABL1 fusion protein, a constitutively active tyrosine kinase that drives leukemogenesis and alters redox homeostasis. These cells are widely used as a model for chronic myelogenous leukemia and for studying BCR-ABL1-mediated signaling pathways, drug responses, and mechanisms of resistance. Their robust growth and well-characterized molecular profile make them an ideal system for functional genomics investigations.
CBR1 encodes NADPH-dependent carbonyl reductase 1, a key enzyme in the detoxification of quinones, prostaglandins, and xenobiotics. CBR1 reduces the anthracycline metabolite doxorubicinol to less cardiotoxic species, directly influencing anticancer drug efficacy. It also metabolizes reactive lipid aldehydes such as 4-hydroxy-2-nonenal, protecting cells from oxidative damage. Transcriptionally, CBR1 is regulated by NRF2 (nuclear factor erythroid 2-related factor 2), the aryl hydrocarbon receptor (AhR), and hypoxia-inducible factor 1-alpha (HIF1A), linking its expression to stress-responsive pathways. CBR1 operates within a network that includes NQO1, AKR1C family members, glutathione S-transferases (GSTs), and the KEAP1-NRF2 axis. By catalyzing NADPH-dependent reduction, CBR1 modulates levels of reactive carbonyls and contributes to prostaglandin metabolism, particularly prostaglandin F2alpha, thereby influencing cellular redox balance and inflammatory signaling.
In the K-562 leukemia background, disruption of CBR1 is anticipated to heighten cellular sensitivity to oxidative stress and anthracycline chemotherapy, given the reliance of these cells on BCR-ABL1-driven redox adaptations. The knockout polyclonal population enables assessment of CBR1??s role in the metabolism of doxorubicin and other carbonyl-containing agents, providing a model to explore mechanisms of drug resistance that are independent of BCR-ABL1 mutation. Furthermore, the interplay between CBR1 loss and the NRF2-regulated antioxidant program can be examined in the context of leukemic oxidative stress, offering insights into how leukemia cells cope with reactive species and therapeutic pressure.
This product supports diverse research applications, including investigation of anthracycline resistance through doxorubicin cytotoxicity assays, evaluation of reactive oxygen species levels using fluorescent probes, and quantification of CBR1 protein and transcript levels via Western blot and RT-qPCR. The cells are also suitable for genome-wide expression profiling by RNA-seq to uncover compensatory mechanisms following CBR1 disruption, and for functional studies of carbonyl metabolism and prostaglandin reduction in a BCR-ABL1-positive model. Enzyme activity assays can directly measure the impact of knockout on carbonyl reduction capacity. These applications facilitate drug sensitivity screening and elucidation of redox-regulated pathways in leukemia. For further information, please contact Ascent Research.
