The CASP6 Knockout K-562 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 human chronic myelogenous leukemia cell line, engineered to disrupt the endogenous CASP6 gene. This product provides a genetically heterogeneous pool of cells with targeted ablation of caspase-6 expression, avoiding clonal selection artifacts and preserving the polyclonal background. The knockout model is validated by western blotting and RT-qPCR to confirm loss of target protein, and is suitable for functional studies requiring a bulk knockout population.
K-562 cells are a widely used Philadelphia chromosome-positive (BCR-ABL1) cell line established from the pleural effusion of a 53-year-old female with chronic myeloid leukemia in blast crisis. These undifferentiated blast cells serve as a model system for hematopoietic differentiation, erythroid maturation, and leukemia biology. Notably, K-562 cells lack BCR-ABL1 kinase inhibitor resistance mutations and retain susceptibility to imatinib, making them valuable for studying BCR-ABL1-mediated signaling and apoptosis.
Caspase-6 is an executioner caspase that plays a critical role in apoptosis, necroptosis, and neurodegeneration. It is activated downstream of initiator caspases such as caspase-8, -9, and -10, and is also processed by caspase-3, forming an amplification loop. Once active, caspase-6 cleaves key cellular substrates including nuclear lamins (lamin A/C), keratin 18, PARP, gelsolin, huntingtin, and tau protein. The enzyme is inhibited by XIAP, which binds and ubiquitinates caspase-6, and it interacts with other apoptotic regulators like caspase-7 and BIRC2/cIAP1. Caspase-6 participates in several signaling pathways, including the apoptosis, p53, TNF, Huntington’s disease, and neurotrophin signaling pathways, where it functions alongside components such as BID, BAX, cytochrome c (CYCS), and APAF1.
In K-562 leukemic cells, knockout of CASP6 disrupts the downstream execution phase of apoptosis, providing a model to dissect caspase-6-dependent cell death mechanisms in a BCR-ABL1-driven hematological malignancy background. Because K-562 cells retain a capacity for differentiation upon induction (e.g., with hemin), the CASP6 knockout can be exploited to investigate the role of caspase-6 in erythroid differentiation and terminal maturation, where non-apoptotic functions of executioner caspases have been implicated. This polyclonal population minimizes the risk of compensatory mutations that may arise in single-cell clones, thus reflecting a more physiologically relevant loss-of-function scenario for pooled screening and population-level assays.
This knockout model is applied in apoptosis and necroptosis research, neurodegenerative disease modeling (Huntington’s, Alzheimer’s), and cancer drug resistance studies. Typical characterization includes western blotting and RT-qPCR to confirm knockout; functional studies employ Annexin V/PI flow cytometry, caspase-6 activity assays, and immunofluorescence. The cells support RNA-seq and differentiation assays with hemin induction, and serve as CRISPR screen controls. For technical support, contact Ascent Research.
