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IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [CUT&RUN]

ABSTRACT: Using CUT&RUN-seq we examined the chromatin occupancy of IKAROS, H3K27-acetylation and CTCF in steady-state growth conditions. IKAROS chromatin occupancy was also assessed after drug-treatment with CC220, VTP-50469 or the drug combination and compared to a DMSO-vehicle treated control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168460 | GEO | 2022/03/10

REPOSITORIES: GEO

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IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia

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IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [ChIP-seq]

Project description:Using ChIP-seq we examined the chromatin occupancy of IKAROS, MENIN, MLL1 and MEIS1 in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines.

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A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia [ChIP-seq]

Project description:Treatment of cells carrying MLL-rearrangements with VTP-50469 (specific Menin-MLL1 inhibitor) displaces Menin from high molecular weight complexes and chromatin genome-wide. Since VTP-50469 block Menin interaction with MLL1 we tested using chip-seq if treatment with VTP-50469 also displaces MLL1 or MLL-fusions from chromatin. We found that the VTP-50469 treatment displaced MLL-fusions from only a subset of MLL-fusion binding sites. Since DOT1L is associated with MLL-AF9 we then tested if displacement of MLL1 also leads to loss of DOT1L association with chromatin on MLL-AF9 binding sites. We found that DOT1L binds to thousands of genes, treatment with VTP-50469 leads to genome wide loss of DOT1L binding including the same subset of MLL-fusion binding sites.

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