The DTNA Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function studies of the DTNA gene. This product provides a genetically heterogeneous pool of K-562 cells carrying targeted disruptions of DTNA, enabling researchers to investigate dystrobrevin alpha function without clonal selection artifacts. The polyclonal format preserves population-level diversity while eliminating functional DTNA protein, making it suitable for bulk assays and functional screens where averaging across multiple knockout alleles is informative.
K-562 is a human bone marrow-derived lymphoblast cell line isolated from a patient with chronic myelogenous leukemia (CML) blast crisis. It is Philadelphia chromosome?Cpositive, expressing the BCR-ABL1 fusion kinase that drives constitutive proliferation and survival signaling. As a multipotent hematopoietic progenitor line, K-562 retains the capacity to differentiate along erythroid, granulocytic, and monocytic lineages under appropriate stimuli. This well-characterized suspension line is widely used as a model for CML biology, hematopoietic differentiation, and adhesion-dependent signaling.
DTNA encodes dystrobrevin alpha, a cytoplasmic scaffold protein that is a core component of the dystrophin-associated glycoprotein complex (DGC). Within this complex, DTNA interacts with dystrophin, utrophin, alpha- and beta-syntrophin, dystroglycan, and the sarcoglycan?Csarcospan subcomplex, bridging the actin cytoskeleton to the extracellular matrix. DTNA signaling is regulated by BCR-ABL1 kinase, integrin adhesion signaling, and Ca2+ influx, and it modulates downstream targets including neuronal nitric oxide synthase (nNOS), GRB2, PI3K, ERK1/2, and actin cytoskeleton reorganization. Knockout of DTNA is hypothesized to uncouple mechanical and signaling linkages transmitted through the DGC, thereby affecting integrin-mediated adhesion and downstream survival pathways.
In the K-562 background, DTNA disruption has particular relevance because BCR-ABL1 oncogenic signaling intersects with adhesion and cytoskeletal organization. Loss of dystrobrevin alpha is expected to impair cell?Csubstrate adhesion and attenuate integrin-dependent activation of Akt and ERK, pathways that promote leukemic cell survival and migration. This model may reveal how the DGC contributes to adhesion-mediated drug resistance, a phenomenon implicated in minimal residual disease and relapse in CML. The DTNA Knockout K-562 Polyclonal Cells thus provide a unique system to dissect the cross-talk between oncogenic kinase signaling and adhesion scaffold proteins in hematopoietic malignancies.
Researchers can employ this knockout model to explore dystrobrevin??s role in hematopoietic cell adhesion and migration, DGC-mediated signal transduction in leukemia, and the consequences of DTNA loss on cytoskeletal dynamics and chemoresistance. Representative experimental approaches include Western blotting and RT-qPCR for target verification, Sanger sequencing to confirm editing, adhesion assays on extracellular matrix proteins, transwell migration assays, immunofluorescence for F-actin organization, flow cytometric analysis of integrin surface expression, phospho-Akt and phospho-ERK profiling, Annexin V apoptosis assays, and imatinib sensitivity testing. For additional information or to inquire about custom gene-edited cell products, please contact Ascent Research.
