DLAT Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for targeted disruption of the DLAT gene in the K-562 chronic myelogenous leukemia cell line. This polyclonal pool provides a heterogeneous loss-of-function model, minimizing clone-specific artifacts and enabling robust functional genomic and metabolic studies. The cells serve as a versatile tool for investigating DLAT-dependent phenotypes without the biases of single-cell cloning.
The K-562 host line originates from the pleural effusion of a 53-year-old female with chronic myelogenous leukemia in blast crisis and harbors the Philadelphia chromosome (BCR-ABL1 fusion). Exhibiting erythroid progenitor-like properties, K-562 cells are widely used as a model for CML, natural killer cell cytotoxicity assays, and hematopoietic research. Their well-characterized oncogenic signaling and rapid growth facilitate gene editing and downstream phenotypic analyses.
DLAT encodes dihydrolipoamide S-acetyltransferase, the E2 subunit of the pyruvate dehydrogenase complex (PDC), which catalyzes the transfer of an acetyl group from lipoamide to coenzyme A, generating acetyl-CoA. This reaction links glycolysis to the citric acid cycle and is tightly regulated by phosphorylation via pyruvate dehydrogenase kinase 1 (PDK1) and dephosphorylation by pyruvate dehydrogenase phosphatase 1 (PDP1). DLAT interacts with PDHA1, PDHB, DLD, and PDHX within the PDC, and its activity is modulated by upstream signals including insulin, HIF1A, MYC, and AMPK. Downstream, acetyl-CoA serves as a substrate for citrate synthesis, NADH production, fatty acid biosynthesis, and histone acetylation, connecting metabolic state to epigenetic regulation.
In K-562 leukemia cells, the BCR-ABL1 oncoprotein drives metabolic reprogramming, enhancing glycolytic flux and altering mitochondrial function. DLAT knockout disrupts the conversion of pyruvate to acetyl-CoA, providing a precise tool to dissect the role of PDC in leukemic proliferation, survival, and adaptation to metabolic stress. This model is particularly valuable for studying how oncogenic signaling rewires central carbon metabolism and for identifying metabolic vulnerabilities that may be exploited therapeutically in CML.
Researchers can employ DLAT Knockout K-562 Polyclonal Cells in metabolic flux analyses using Seahorse technology, PDH activity assays, and acetyl-CoA quantification. The polyclonal knockout population is compatible with western blotting, RT-qPCR, RNA-seq, and flow cytometry for target validation and downstream pathway analysis. Applications extend to high-throughput drug screening for PDC modulators, mitochondrial disease modeling, and biomarker discovery. For additional product information or technical support, please contact Ascent Research.
