The BCL9L Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population targeting the BCL9L gene. This heterogeneous pool of loss-of-function alleles is generated without single-cell cloning, minimizing clonal bias and providing a robust model for functional studies. The polyclonal format is ideal for experiments requiring gene disruption rather than isogenic uniformity, such as pathway dissection and drug target validation.
HAP1 is a near-haploid human chronic myeloid leukemia (CML) cell line derived from KBM-7. Its haploid karyotype, with only one copy of each chromosome, facilitates efficient CRISPR/Cas9 editing and unambiguous genotype-phenotype analysis. Widely employed in functional genomics and knockout screening, HAP1 cells retain hematopoietic lineage characteristics and serve as a tractable model for studying Wnt signaling and leukemogenesis.
BCL9L functions as a transcriptional coactivator in the canonical Wnt/??-catenin pathway, directly interacting with ??-catenin and the PYGO adaptors (PYGO1/2). Following Wnt ligand (e.g., Wnt3a, Wnt1)-induced stabilization of ??-catenin and its nuclear translocation, ??-catenin associates with TCF/LEF transcription factors such as TCF4. The ??-catenin?CBCL9L?CPYGO complex then potently activates transcription of Wnt target genes, including the proliferation drivers MYC and CCND1 and the pathway feedback regulators AXIN2 and LGR5.
Disruption of BCL9L in HAP1 cells selectively impairs ??-catenin-dependent transactivation without altering upstream signal relay, providing a clean system to study coactivator-specific functions. This model is relevant to hematopoietic malignancies, as aberrant Wnt activity is implicated in CML and acute lymphoblastic leukemia. Moreover, it allows researchers to investigate BCL9L’s contribution to oncogenic transcription in colorectal cancer and multiple myeloma settings.
Standard readouts include Western blotting for BCL9L and target proteins, RT?qPCR for downstream transcripts, and TOP/FOP luciferase assays to gauge Wnt pathway activity. Co-immunoprecipitation validates complex formation, while cell viability and drug sensitivity profiles inform drug target validation and synthetic lethality screens. The polyclonal nature also enables pooled CRISPR screening for genetic interactions. For inquiries, please contact Ascent Research.
