The CBR3 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 human chronic myelogenous leukemia cell line, designed to disrupt the CBR3 gene locus. This product provides a heterogeneous pool of cells with targeted gene inactivation, facilitating the study of CBR3 loss-of-function without the clonal selection artifacts inherent in monoclonal lines. The polyclonal format captures diverse genetic edits across the population, enabling robust assessment of gene function in a model system that more closely reflects biological variability.
K-562 cells were originally isolated from the pleural effusion of a 53-year-old female with chronic myelogenous leukemia in blast crisis. These suspension-adapted lymphoblastoid cells are highly undifferentiated and Philadelphia chromosome positive, expressing the BCR-ABL1 fusion oncogene. K-562 serves as a widely used model for hematopoietic malignancies, erythropoiesis, and drug resistance mechanisms. The cell line’s constitutive BCR-ABL1 signaling and altered redox state make it an ideal host for investigating genes involved in detoxification and oxidative stress responses.
CBR3 encodes an NADPH-dependent carbonyl reductase that catalyzes the reduction of diverse endogenous and xenobiotic carbonyl compounds to their corresponding alcohols. This enzyme plays a critical role in cellular detoxification and redox homeostasis, with established functions in prostaglandin metabolism and the inactivation of cytotoxic aldehydes. CBR3 is transcriptionally upregulated by NRF2 (NFE2L2) in response to oxidative stress, hypoxia, and xenobiotic stimuli. It operates downstream of NRF2 and interacts with NADPH as an obligate cofactor, utilizing reducing equivalents derived from the pentose phosphate pathway. Key substrates include the anthracycline chemotherapeutic doxorubicin, and CBR3-mediated reduction of such carbonyls generates less reactive alcohol metabolites, thereby diminishing reactive oxygen species formation and protecting cells from oxidative damage.
In the K-562 leukemia background, disruption of CBR3 is expected to alter the cell’s capacity to detoxify electrophilic carbonyl compounds, potentially sensitizing them to agents such as doxorubicin and other carbonyl-containing drugs. The BCR-ABL1-driven oncogenic signaling in K-562 cells elevates basal oxidative stress, and loss of CBR3 may further impair redox balance, leading to increased susceptibility to apoptosis or altered differentiation. This knockout model thus provides a powerful tool for dissecting chemoresistance pathways and the role of carbonyl reduction in leukemia cell survival.
This cell model is suited for a range of research applications, including drug metabolism studies, investigation of chemoresistance mechanisms, oxidative stress modeling, and toxicology testing. Typical experimental workflows involve validation of knockout efficiency via western blotting and RT-qPCR for CBR3, assessment of cellular sensitivity to doxorubicin using viability assays such as MTT/XTT or flow cytometry for apoptosis, and measurement of reactive oxygen species levels and the NADPH/NADP+ ratio. For further information or to discuss experimental design using these cells, please contact Ascent Research.
