The BCL2L1 Knockout HAP1 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal cell population derived from the near-haploid human HAP1 cell line, engineered for disruption of the BCL2L1 gene. This pool maintains the genetic heterogeneity of a polyclonal knockout model, facilitating the study of Bcl-xL function without clonal bias.
HAP1 originates from the KBM-7 chronic myeloid leukemia cell line and retains a near-haploid karyotype, except for a disomic region of chromosome 15. Its simplified genome makes it an ideal host for haploid genetic screens and CRISPR-based functional genomics, while its leukemic background offers a relevant context for cancer biology research.
BCL2L1 encodes Bcl-xL, a critical anti-apoptotic protein that binds and sequesters the pro-apoptotic effectors BAK and BAX, preventing mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release. Under apoptotic stress, BH3-only proteins BAD, BIM, PUMA, and NOXA displace BAK/BAX, triggering MOMP and activating the caspase-9?Ccaspase-3 cascade via APAF1. BCL2L1 expression is transcriptionally upregulated by STAT5, STAT3, NF-??B, and CREB downstream of cytokines (IL-3, Epo) and the PI3K/AKT and JAK2 pathways. Bcl-xL also interacts with VDAC, IP3R, and Beclin-1, linking it to mitochondrial metabolism and autophagy.
Knocking out BCL2L1 in HAP1 cells eliminates a key survival checkpoint, sensitizing them to intrinsic apoptosis and enabling dissection of death-signaling networks. The haploid configuration ensures unambiguous loss-of-function phenotypes, making the model valuable for studying the interplay between survival pathways??JAK/STAT, PI3K/AKT??and mitochondrial apoptosis, as well as for exploring drug resistance mechanisms dependent on Bcl-xL.
These polyclonal knockout cells are suitable for apoptosis assays including annexin V/PI flow cytometry, cytochrome c release measurement, and caspase activity profiling. They are ideal for synthetic lethality screens, BH3 profiling, and validation of Bcl-xL inhibitors using cell viability assays like CellTiter-Glo. Co-immunoprecipitation and Western blotting enable interaction and expression studies, while RT-qPCR confirms transcriptional changes. The model also supports drug sensitivity testing, offering a platform for cancer and apoptosis research. For further details, contact Ascent Research.
