The IDH2 Knockout Jurkat Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the IDH2 gene has been disrupted to abolish expression of mitochondrial isocitrate dehydrogenase 2. This model is generated in the Jurkat human T lymphocyte leukemia cell line, providing a heterogeneous population of cells carrying various CRISPR-induced mutations at the target locus. The polyclonal format captures a spectrum of loss-of-function alleles, enabling robust population-level analyses of metabolic and signaling disruptions without the clonal selection bias inherent in monoclonal derivatives. This product is well-suited for applications requiring a representative knockout model in a leukemic T-cell background, including functional genomics, metabolic profiling, and drug-target validation studies.
Jurkat cells are derived from an acute T-cell leukemia patient and have been extensively characterized as a model for T-cell receptor signaling, apoptosis, and leukemogenesis. They express key T-lineage markers and exhibit rapid growth in suspension culture, making them ideal for high-throughput assays. The Jurkat background offers a physiologically relevant context for studying IDH2 function, as T lymphocytes rely on metabolic reprogramming for activation and survival. Moreover, Jurkat cells are widely used in cancer biology research to dissect oncogenic pathways, and their human origin ensures direct translational relevance to clinical settings involving hematological malignancies.
IDH2 encodes a homodimeric, NADP+-dependent enzyme that catalyzes the oxidative decarboxylation of isocitrate to ??-ketoglutarate within the mitochondrial matrix, concurrently generating NADPH. This reaction is a critical component of the tricarboxylic acid (TCA) cycle and serves as a key source of reducing equivalents for cellular antioxidant systems and biosynthetic processes. IDH2 activity is regulated by upstream factors including HIF1A, NFE2L2, and SIRT3, which modulate expression or post-translational modifications. Downstream, IDH2 influences HIF1A stabilization, the activity of ??-ketoglutarate-dependent dioxygenases, histone methylation patterns, and the NADPH/NADP+ redox balance. It interacts directly with NADP+ and isocitrate, and its mitochondrial import depends on specific receptors. Representative pathway components operating in concert with IDH2 include IDH3, citrate synthase (CS), aconitase 2 (ACO2), and oxoglutarate dehydrogenase (OGDH).
In the Jurkat T-cell leukemia context, CRISPR-mediated knockout of IDH2 disrupts mitochondrial TCA cycle flux and attenuates NADPH production, leading to altered redox homeostasis and potential stabilization of HIF1A. This metabolic reprogramming can impair proliferation and sensitize cells to oxidative stress, mirroring metabolic vulnerabilities observed in IDH2-mutant malignancies such as acute myeloid leukemia and glioma. The polyclonal knockout cells therefore serve as a versatile platform for dissecting the tumor-suppressive or oncogenic roles of IDH2 loss in a leukemic background, enabling researchers to explore how metabolic enzyme deficiency influences T-cell transformation, survival, and response to therapy.
This knockout model is optimized for a range of advanced research applications, including metabolic dependency studies using Seahorse flux analysis and LC-MS-based metabolomics, functional analyses of IDH2 in T-cell signaling via RT-qPCR and Western blotting, and high-throughput screening of IDH2-targeted therapies. Additional assays such as flow cytometry for viability and apoptosis, ROS detection, and cell proliferation assays (MTS/MTT) are directly compatible. The polyclonal nature allows robust evaluation of population-level metabolic shifts and drug sensitivity. For further product details, technical support, or custom inquiries, please contact Ascent Research.
