DOCK10 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human DOCK10 gene. This product consists of a heterogeneous pool of HAP1 cells carrying diverse loss-of-function mutations induced by CRISPR/Cas9-mediated gene disruption. The polyclonal format preserves population-level diversity and is suited for pooled screens and studies where clonal variation reflects biological heterogeneity. It provides a robust DOCK10 loss-of-function model without single-cell cloning.
The HAP1 cell line is a near-haploid human chronic myeloid leukemia (CML) model derived from KBM-7 cells. Its haploid karyotype enables efficient gene knockout as disruption of a single allele abolishes gene function. HAP1 retains key CML features, including dependency on BCR-ABL signaling, offering a disease-relevant platform for functional genomics. This genetic tractability makes HAP1 a preferred background for investigating genes involved in hematopoietic neoplasia and drug responses.
DOCK10 encodes a guanine nucleotide exchange factor (GEF) that activates Rho GTPases Rac1 and Cdc42 by exchanging GDP for GTP. These GTPases trigger downstream effectors such as PAK kinases and the WAVE complex, which stimulate Arp2/3-mediated actin polymerization. DOCK10 relays signals from chemokine receptors, integrins, and PI3K, interacting with the PI3K regulatory subunit p85 to remodel the actin cytoskeleton. This signaling cascade drives lamellipodia formation, cell migration, and adhesion dynamics, positioning DOCK10 as a central coordinator of cytoskeletal reorganization and cell motility.
In the HAP1 CML background, DOCK10 disruption helps elucidate how Rho GTPase activation contributes to leukemic cell behavior. Aberrant DOCK10-Rac1/Cdc42 signaling may promote CML cell invasion, adhesion, and survival, processes crucial for disease progression. By using near-haploid cells, researchers can cleanly interrogate DOCK10 function without compensatory signaling from redundant alleles. This knockout model enables dissection of DOCK10-dependent mechanisms in the context of BCR-ABL-driven oncogenesis, potentially uncovering therapeutic targets for overcoming drug resistance and metastatic dissemination.
Applications include Transwell migration assays, wound healing, phalloidin staining for F-actin, and Rac1/Cdc42 activation pull-downs. The polyclonal population facilitates high-throughput genetic screens, drug target validation, and investigation of DOCK10 in immune cell trafficking and cancer invasion. Researchers can employ these cells in pooled CRISPR screens, fluorescence microscopy of actin dynamics, and flow cytometry for adhesion markers, integrating DOCK10 loss-of-function into broader pathway analyses. For more information, please contact Ascent Research.
