Similar Datasets
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025271 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025232 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025227 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025272 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025230 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025229 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025228 | Pride
Project description:Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription.
2022-03-11 | PXD025231 | Pride
Project description:Using RNA-seq we examined the transcriptional changes following IKAROS degradation, MENIN-inhibition or the drug combination in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines and the CBAM-68552 patient-derived xenograft model.
2022-03-10 | GSE168462 | GEO
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.
2022-03-10 | GSE168461 | GEO