Similar Datasets
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE302494 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273654 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273653 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273651 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273648 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273647 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273643 | GEO
Project description:Leukemia stem cells (LSCs) give rise to mature leukemia blasts and are the major cause of therapy resistance and relapse in acute myeloid leukemia (AML). We propose a novel strategy to eliminate heterogeneous LSCs but spare hematopoietic stem cells (HSCs) by targeting essential genes that are highly expressed in LSCs than that in HSCs. Nucleoporin 214 (NUP214) is determined as a dose-dependently essential gene (DDEG) in LSCs. Homozygous deletion of Nup214 eliminates LSCs and HSCs; however, Nup214 haploinsufficiency impairs LSC maintenance but spares HSCs by selectively inducing ferroptosis of LSCs. Mechanistically, NUP214 locates to chromatin and interacted with Sub1 to inhibit the transcription of heme oxygenase-1 (Hmox1) and arachidonate 15-lipoxygenase (Alox15), thus protecting LSCs against lipid peroxidation. We screened and identified a small molecule 0449-b as a molecular glue that links NUP214 and an NEDD8 E3 ligase, Rbx2, to induce neddylation and degradation of NUP214. 0449-b shows efficacy in selective eradication of LSCs but has a negligible effect on normal hematopoietic stem and progenitor cells. These biological and chemical findings provide a valuable strategy to eliminate LSCs by targeting DDEGs.
2025-07-29 | GSE273642 | GEO
Project description:To profile the E3 ligase associated with NUP214 neddylation, the NUP214 co-IP sample in THP-1 cells were examined by mass spectrometry.
2025-07-26 | PXD054462 | Pride
Project description:To illustrate NUP214-interacting proteins, we performed co-immunoprecipitation (co-IP) followed by mass spectrometry using MLL-AF9-driven LSCs to characterize protein interactomes of NUP214.
2025-07-26 | PXD054438 | Pride