The KDM1A Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HAP1 human chronic myeloid leukemia cell line, designed to disrupt the KDM1A gene and eliminate its histone demethylase activity. This polyclonal format provides a heterogeneous pool of cells carrying targeted gene disruption, enabling robust loss-of-function studies without the clonal selection bias inherent to single-cell-derived lines. The product serves as a powerful tool for investigating KDM1A-dependent epigenetic regulation in a leukemia-relevant context.
HAP1 is a near-haploid human cell line originally derived from KBM-7 chronic myeloid leukemia cells. Its haploid genome simplifies genetic manipulation and functional genomics, making it a preferred model for haploid genetic screens, drug target validation, and mechanistic studies in hematological malignancies. The adherent growth and stable karyotype of HAP1 cells facilitate high-throughput screening and reproducible experimental workflows, providing a reliable platform for interrogating gene function.
KDM1A (LSD1) encodes a histone demethylase that specifically removes mono- and dimethyl groups from lysine 4 and lysine 9 of histone H3 (H3K4me1/2 and H3K9me1/2), acting as a transcriptional corepressor or coactivator depending on cellular context. In complex with CoREST (RCOR1) and HDAC1/2, KDM1A represses transcription by demethylating H3K4 at target gene promoters. Upstream regulators include the REST corepressor complex and growth factor signaling pathways such as TGF-??, EGF, and BCR-ABL. KDM1A directly modulates expression of downstream targets like CDKN1A (p21), MYC, CDH1 (E-cadherin), and VIM (vimentin), and it interacts with the NuRD complex, SNAI1, and the FAD cofactor to control stemness genes NANOG and OCT4.
In HAP1 leukemia-derived cells, KDM1A knockout leads to elevated H3K4me2 and H3K9me2 levels at target gene promoters, disrupting oncogenic transcriptional programs. This loss of function impairs cell proliferation, survival, and differentiation, potentially reversing leukemic phenotypes. The haploid background ensures that disruption of a single KDM1A allele directly impacts the phenotype, avoiding compensation from a second allele. Consequently, this polyclonal knockout model is particularly valuable for studying epigenetic dependencies in chronic myeloid leukemia and for performing genetic interaction screens to identify synthetic lethal partners.
This product supports a wide range of applications, including functional validation of KDM1A in leukemia, drug target identification, and investigation of epigenetic mechanisms. It is suitable for high-throughput chemical screening to discover LSD1 modulators and for haploid genetic screens to map KDM1A-linked pathways. Representative assays include Western blotting for KDM1A and histone marks, RT-qPCR for target genes such as MYC and CDKN1A, ChIP-qPCR for H3K4me2 occupancy, cell viability and apoptosis assays, colony formation, flow cytometry for differentiation markers, and drug sensitivity profiling. For further information or technical support, please contact Ascent Research.
