The DOCK2 Knockout K-562 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population in which the DOCK2 gene has been disrupted via CRISPR/Cas9-mediated gene targeting. This product offers a loss-of-function model in the K-562 human chronic myeloid leukemia cell line, a widely used hematopoietic progenitor system. The polyclonal format preserves a heterogeneous array of genetic alterations, minimizing clonal bias and enabling robust pooled functional analyses. As a ready-to-use tool, these cells provide a consistent and practical resource for investigating DOCK2-dependent processes in a malignant hematopoietic background.
The host K-562 cell line was originally derived from the pleural effusion of a patient with chronic myeloid leukemia in blast crisis. It carries the Philadelphia chromosome, giving rise to the oncogenic BCR-ABL fusion protein with constitutive tyrosine kinase activity. K-562 cells exhibit features of hematopoietic progenitors and can undergo erythroid and megakaryocytic differentiation under appropriate stimuli. Their well-characterized signaling network and ease of culture make them a standard model for studying leukemia biology, signal transduction, and drug responses in hematologic malignancies.
DOCK2 serves as a hematopoietic cell-specific guanine nucleotide exchange factor that activates the small GTPases Rac1 and Rac2 downstream of chemokine receptors such as CXCR4 and CCR7, as well as immune receptors including the T cell receptor (TCR) and B cell receptor (BCR). Upon receiving upstream signals from phosphoinositide 3-kinase (PI3K) and its lipid product PIP3, DOCK2 forms complexes with ELMO1 and CRK, catalyzing GDP/GTP exchange on Rac. Activated Rac then triggers p21-activated kinase (PAK), c-Jun N-terminal kinase (JNK), and the NF-??B pathway, ultimately promoting actin polymerization and cytoskeletal reorganization. This cascade is essential for directed cell migration, immune synapse formation, and lymphocyte activation, integrating cues from cytokines such as IL-2.
In the context of K-562 leukemia cells, DOCK2 disruption allows dissection of its role in malignant signaling networks that intersect with BCR-ABL-driven pathways. Since K-562 cells exhibit elevated Rac activity that may partly depend on DOCK2, this knockout model helps clarify whether DOCK2-mediated Rac activation cooperates with or operates independently of the BCR-ABL kinase cascade in regulating migration, adhesion, and survival. Moreover, germline DOCK2 mutations cause combined immunodeficiency and autoimmune manifestations, highlighting the gene??s importance in immune cell function. Thus, the model is clinically relevant for understanding hematologic malignancy and immune dysregulation.
Researchers can utilize these polyclonal knockout cells to examine Rac-dependent actin dynamics using phalloidin staining and Rac activation pull-down assays. Transwell migration and chemotaxis assays enable quantitative assessment of directional cell movement, while flow cytometry and phospho-protein western blotting (e.g., for PAK and JNK) reveal signaling perturbations. The cells are suited for chemokine signaling pathway screens and for validating inhibitors targeting the DOCK2?CRac axis. Comparative studies with wild-type K-562 cells facilitate investigation of leukemia?Cimmune signaling crosstalk, aiding drug discovery in hematopoietic cancers and immunotherapy. For further details or custom requests, please contact Ascent Research.
