LDHA Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte cell line. This product offers a loss-of-function model for studying lactate dehydrogenase A (LDHA) in the context of human B cell biology and cancer metabolism. The polyclonal nature of the knockout population ensures representation of multiple gene disruption events, facilitating robust functional studies without selection for individual clones.
The Raji cell line, originally isolated from a Burkitt’s lymphoma patient, serves as a well-characterized model for B lymphocyte function, including antibody production and antigen presentation. These Epstein-Barr virus (EBV)-positive cells exhibit a highly glycolytic metabolism, characteristic of many aggressive lymphomas, making them particularly suitable for investigating the Warburg effect and metabolic dependencies in lymphomagenesis.
LDHA catalyzes the conversion of pyruvate to lactate during glycolysis, a critical step that regenerates NAD+ to sustain glycolytic flux and supports rapid cellular proliferation. Its expression is transcriptionally regulated by HIF1A and MYC downstream of PI3K/AKT signaling, linking oncogenic pathways to metabolic reprogramming. LDHA forms heterotetramers with LDHB, and its activity drives lactate production and subsequent monocarboxylate transporter 4 (MCT4)-mediated lactate export, contributing to tumor microenvironment acidification. In the broader glycolytic pathway, LDHA functions downstream of glucose uptake via GLUT1 and the sequential actions of hexokinase, phosphofructokinase, and pyruvate kinase M2.
Disruption of LDHA in Raji cells abolishes the enzymatic conversion of pyruvate to lactate, disrupting glycolytic flux and attenuating the Warburg effect. This loss-of-function model impairs the cells’ ability to sustain rapid proliferation and may sensitize them to oxidative stress due to diminished NAD+ regeneration. Given the reliance of Burkitt’s lymphoma cells on aerobic glycolysis, this knockout provides a valuable system to dissect the metabolic vulnerabilities of aggressive B cell malignancies and the role of lactate in shaping the immunosuppressive tumor microenvironment.
Researchers can employ these polyclonal knockout cells in diverse experimental contexts, including western blotting and RT-qPCR for target validation, lactate production assays to quantify metabolic output, and Seahorse XF glycolysis stress tests to assess glycolytic function. Paired with proliferation and apoptosis assays, the model enables investigation of LDHA-dependent growth control. Drug sensitivity studies using glycolytic inhibitors further facilitate target validation and therapeutic exploration. For more information, please contact Ascent Research.
