ASXL1 Knockout OCI-AML3 Cell Line

The choice depends on whether you are studying ASXL1 (additional sex combs like 1)'s role as a Polycomb-related epigenetic regulator or modeling ASXL1-mutated MDS/AML and Bohring-Opitz syndrome. The Knockout line is the standard tool for asking whether ASXL1 is required for these processes — ASXL1 is a member of the PR-DUB (Polycomb repressive deubiquitinase) complex with BAP1, deubiquitinating H2AK119ub (the PRC1 mark); ASXL1 has emerged as one of the most frequently mutated genes in MDS, AML, and CHIP (clonal hematopoiesis of indeterminate potential), typically as truncating mutations generating gain-of-function ASXL1 fragments. Overexpression is useful for studying ASXL1 gain-of-function effects. For hematologic malignancy research, the EDITGENE ASXL1 Knockout in OCI-AML3 is uniquely valuable — OCI-AML3 is an NPM1c/DNMT3A R882C-mutant AML cell line, providing a clinically representative AML context. Rescue with wild-type or truncating ASXL1 mutants (Y591X, R693X, others) enables disease modeling — these truncations are characteristic of MDS/AML and confer dominant gain-of-function. ASXL1 de novo missense mutations cause Bohring-Opitz syndrome. The knockout is valuable for studying H2AK119ub epigenetic regulation, CHIP biology, and emerging AML therapy approaches in ASXL1-mutated contexts.

Primary applications: • PR-DUB complex: BAP1-ASXL1 deubiquitinase complex assembly and H2AK119ub levels analysis in ASXL1-null cells. • ASXL1 truncation modeling: rescue with Y591X, R693X, or other patient-derived truncating ASXL1 mutations for genotype-function studies of MDS/AML and CHIP. • NPM1c AML context: in OCI-AML3 background (NPM1c, DNMT3A R882C), characterization of ASXL1-mutation-driven leukemia biology. • Bohring-Opitz syndrome modeling: rescue with de novo ASXL1 missense mutations for developmental disorder studies. • Menin-MLL inhibitor combination: revumenib/SNDX-5613, ziftomenib/KO-539 combination with ASXL1 status studies. EDITGENE recommends this OCI-AML3 model for researchers investigating ASXL1-mutated AML/MDS biology and clinically relevant AML therapy development.

Yes, with critical considerations for ASXL1's dominant gain-of-function truncation biology: • Construct design: use a codon-modified ASXL1 sequence with a small C-terminal tag (FLAG, HA). ASXL1 has N-terminal HARE-HTH and ASXM domains, central PHD finger, and C-terminal PHD finger — preserve all elements for full-length rescue. • Truncating mutation rescue: ⭐⭐ Y591X, R693X, G646Wfs*12, and other patient-derived truncations enable disease modeling — these truncations confer dominant gain-of-function, recruiting BAP1 to inappropriate genomic sites. • ASXM-mutant rescue: ASXM domain mutations affect BAP1 interaction. • Functional readout: rescue should restore H2AK119ub levels and PR-DUB complex function; truncating mutants should recapitulate disease-associated H2AK119ub redistribution. OCI-AML3-specific considerations: • OCI-AML3 is a human acute myeloid leukemia cell line with two clinically important mutations: NPM1 type A mutation (NPM1c, cytoplasmic mislocalization) and DNMT3A R882C — making it one of the most clinically representative AML cell lines. • Lentiviral transduction is supported with moderate efficiency. • OCI-AML3's mutation profile is relevant for studying NPM1c AML biology and emerging menin-MLL inhibitor (revumenib/SNDX-5613, ziftomenib/KO-539) targeted therapy.