Expression analysis of Mll3 knockdown p53-/- HSPC vs. control p53-/- HSPC
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ABSTRACT: Recurring deletions of chromosome 7 and 7q [-7/del(7q)] occur in myelodysplastic syndromes and acute myeloid leukemia (AML) and are associated with poor prognosis. However, the identity of specific tumor suppressors on 7q remains elusive. Using RNAi and CRISPR/Cas9 approaches, we show that a ~50% reduction in gene dosage of the mixed lineage leukemia 3 (MLL3) gene, located on 7q36.1, cooperates with other events occurring in -7/del(7q) AMLs to promote leukemogenesis. Mll3 suppression impairs the differentiation of HSPC. Interestingly, Mll3 suppressed leukemias, like human -7/del(7q) AMLs, are refractory to conventional chemotherapy but sensitive to the BET inhibitor JQ1. Thus, our mouse model functionally validates MLL3 as a haploinsufficient 7q tumor suppressor, and suggests a therapeutic option for this aggressive disease.
ORGANISM(S): Mus musculus
PROVIDER: GSE54313 | GEO | 2014/03/19
SECONDARY ACCESSION(S): PRJNA236139
REPOSITORIES: GEO
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