The DPP9 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 host line, with disruption of the DPP9 gene to abolish functional protein expression. This polyclonal pool, generated via CRISPR/Cas9-mediated gene targeting, provides a heterogeneous loss-of-function model that avoids clonal selection bias, enabling robust analysis of DPP9-dependent processes.
The K-562 cell line is a suspension lymphoblast line derived from a 53-year-old female with BCR-ABL-positive chronic myelogenous leukemia in blast crisis. It serves as a model for hematopoietic differentiation and blast crisis pathophysiology, characterized by constitutive tyrosine kinase activity and uniform growth in suspension, facilitating large-scale experimental manipulation.
DPP9 encodes a cytoplasmic post-proline dipeptidyl aminopeptidase that cleaves N-terminal dipeptides from proline-containing peptides, regulating bioactive molecules like neuropeptide Y (NPY) and glucagon-like peptide-1 (GLP-1). The enzyme is a key regulator of the NLRP1 inflammasome: DPP9 inhibition or deletion releases NLRP1 autoinhibition, promoting ASC-dependent caspase-1 activation and consequent pyroptosis with IL-1?? release. DPP9 is transcriptionally controlled by NF-??B downstream of TNF-?? and IL-1??, and interacts with DPP8, linking it to peptide hormone metabolism and G-protein coupled receptor pathways.
In the K-562 leukemic background, DPP9 knockout enables dissection of crosstalk between BCR-ABL oncogenic signaling and innate immune responses. The constitutive proliferation signals in these cells provide a context to examine how inflammasome-driven pyroptosis and cytokine secretion influence leukemic cell survival and tumor microenvironment dynamics. The suspension format additionally supports high-throughput screening assays for peptide hormone regulation and cell death studies.
Applications include mechanistic investigation of NLRP1 inflammasome activation, DPP9 inhibitor screening for anti-inflammatory therapy, peptide hormone regulation studies, and tumor microenvironment modeling. Typical assays with this model encompass western blotting for NLRP1, caspase-1, and IL-1??; RT-qPCR for DPP9 expression; immunofluorescence for ASC speck formation; flow cytometry for pyroptosis (PI uptake); DPP9 enzymatic activity measurement with fluorogenic substrates; ELISA for IL-1?? secretion; and Sanger sequencing or T7E1 assay for knockout validation. These polyclonal cells support drug discovery and mechanistic research across immunology and cancer biology. For additional information, please contact Ascent Research.
