The GSTM2 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population targeting the GSTM2 gene in the near-haploid human HAP1 cell line. This loss-of-function model is created via CRISPR/Cas9-mediated gene disruption, resulting in a heterogeneous pool of cells without clonal isolation. The product enables robust population-level analysis of GSTM2’s role in detoxification, oxidative stress response, and cancer biology, avoiding biases from single-cell clones.
HAP1 cells are derived from the KBM-7 chronic myeloid leukemia (CML) line and possess a near-haploid karyotype, which facilitates straightforward genetic engineering and homozygous gene targeting. As hematopoietic progenitor cells, they provide a cancer-relevant context for studying leukemia biology and drug resistance. The near-haploid background minimizes paralogous compensation, making HAP1 an optimal host for dissecting the functions of detoxification genes like GSTM2 in a clean genetic background.
GSTM2 encodes a glutathione S-transferase mu 2 enzyme that conjugates reduced glutathione to electrophilic xenobiotics and endogenous metabolites, a key step in Phase II detoxification. Its expression is transcriptionally activated by NRF2 and inhibited by KEAP1, integrating signals from oxidative stress and electrophilic compounds. GSTM2 also binds ASK1, suppressing ASK1-mediated apoptotic signaling under oxidative conditions. Downstream, it reduces reactive oxygen species and protects cellular macromolecules, thereby modulating chemoresistance and redox homeostasis within the glutathione metabolism network.
In HAP1 cells, GSTM2 knockout allows unambiguous assessment of glutathione-mediated detoxification pathways in the context of CML-derived hematopoiesis. The near-haploid state eliminates redundancy from diploid genomes, enabling direct investigation of how GSTM2 loss affects NRF2-driven transcriptional responses, ASK1-dependent apoptosis, and sensitivity to chemotherapeutics. This model is well-suited for studies linking phase II metabolism to leukemia drug resistance and for synthetic lethality screens that uncover vulnerabilities in detoxification-compromised cells.
Researchers can utilize these cells in a variety of assays, including GST activity measurements with 1-chloro-2,4-dinitrobenzene (CDNB), intracellular ROS detection, drug sensitivity profiling, Western blotting, and RT-qPCR for pathway components. The polyclonal format supports population-based readouts, facilitating high-throughput screening and averaging across genetic variants. Applications encompass xenobiotic metabolism research, oxidative stress biology, cancer genetics, and genetic toxicology. For further experimental support, please contact Ascent Research.
