Similar Datasets
Project description: Not available
| S-EPMC4362230 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-11-14 | GSE267473 | GEO
Project description:Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) initiation, relapse, and chemoresistance, yet the core post-translational events governing LSC formation and maintenance remain elusive. Here, through phosphoproteomic profiling of normal hematopoietic stem and progenitor cells (HSPCs) versus LSC-enriched population, we identify DEK phosphorylation as a critical modification during leukemogenesis. Functional studies in MLL-AF9- and HOXA9/MEIS1-driven AML mouse models, as well as patient-derived xenografts (PDXs), demonstrate that DEK deficiency impairs LSC maintenance and AML development. Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Mechanistically, DEK recruits the transcription factor GABPA to drive overexpression of transcriptional cofactor PBX3, a key oncogenic driver in AML, thereby sustaining a leukemogenic transcriptional program. This DEK-GABPA interaction strictly depends on DEK phosphorylation at Ser301/303/306/307 (the 4S site), which stabilizes the conformation of the DEK-GABPA complex. We demonstrate CK2 as the upstream kinase that directly phosphorylates DEK-4S site. Importantly, inhibition of DEK phosphorylation through 4S site mutations or treatment with a clinical-stage CK2 inhibitor CX-4945 selectively depletes LSCs while sparing normal HSPCs. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and suppresses the PBX3-mediated leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy in AML.
2025-09-30 | GSE309284 | GEO
Project description:Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) initiation, relapse, and chemoresistance, yet the core post-translational events governing LSC formation and maintenance remain elusive. Here, through phosphoproteomic profiling of normal hematopoietic stem and progenitor cells (HSPCs) versus LSC-enriched population, we identify DEK phosphorylation as a critical modification during leukemogenesis. Functional studies in MLL-AF9- and HOXA9/MEIS1-driven AML mouse models, as well as patient-derived xenografts (PDXs), demonstrate that DEK deficiency impairs LSC maintenance and AML development. Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Mechanistically, DEK recruits the transcription factor GABPA to drive overexpression of transcriptional cofactor PBX3, a key oncogenic driver in AML, thereby sustaining a leukemogenic transcriptional program. This DEK-GABPA interaction strictly depends on DEK phosphorylation at Ser301/303/306/307 (the 4S site), which stabilizes the conformation of the DEK-GABPA complex. We demonstrate CK2 as the upstream kinase that directly phosphorylates DEK-4S site. Importantly, inhibition of DEK phosphorylation through 4S site mutations or treatment with a clinical-stage CK2 inhibitor CX-4945 selectively depletes LSCs while sparing normal HSPCs. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and suppresses the PBX3-mediated leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy in AML.
2025-09-30 | GSE309177 | GEO
Project description:Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) initiation, relapse, and chemoresistance, yet the core post-translational events governing LSC formation and maintenance remain elusive. Here, through phosphoproteomic profiling of normal hematopoietic stem and progenitor cells (HSPCs) versus LSC-enriched population, we identify DEK phosphorylation as a critical modification during leukemogenesis. Functional studies in MLL-AF9- and HOXA9/MEIS1-driven AML mouse models, as well as patient-derived xenografts (PDXs), demonstrate that DEK deficiency impairs LSC maintenance and AML development. Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Mechanistically, DEK recruits the transcription factor GABPA to drive overexpression of transcriptional cofactor PBX3, a key oncogenic driver in AML, thereby sustaining a leukemogenic transcriptional program. This DEK-GABPA interaction strictly depends on DEK phosphorylation at Ser301/303/306/307 (the 4S site), which stabilizes the conformation of the DEK-GABPA complex. We demonstrate CK2 as the upstream kinase that directly phosphorylates DEK-4S site. Importantly, inhibition of DEK phosphorylation through 4S site mutations or treatment with a clinical-stage CK2 inhibitor CX-4945 selectively depletes LSCs while sparing normal HSPCs. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and suppresses the PBX3-mediated leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy in AML.
2026-04-28 | GSE329274 | GEO
Project description:Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) initiation, relapse, and chemoresistance, yet the core post-translational events governing LSC formation and maintenance remain elusive. Here, through phosphoproteomic profiling of normal hematopoietic stem and progenitor cells (HSPCs) versus LSC-enriched population, we identify DEK phosphorylation as a critical modification during leukemogenesis. Functional studies in MLL-AF9- and HOXA9/MEIS1-driven AML mouse models, as well as patient-derived xenografts (PDXs), demonstrate that DEK deficiency impairs LSC maintenance and AML development. Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Mechanistically, DEK recruits the transcription factor GABPA to drive overexpression of transcriptional cofactor PBX3, a key oncogenic driver in AML, thereby sustaining a leukemogenic transcriptional program. This DEK-GABPA interaction strictly depends on DEK phosphorylation at Ser301/303/306/307 (the 4S site), which stabilizes the conformation of the DEK-GABPA complex. We demonstrate CK2 as the upstream kinase that directly phosphorylates DEK-4S site. Importantly, inhibition of DEK phosphorylation through 4S site mutations or treatment with a clinical-stage CK2 inhibitor CX-4945 selectively depletes LSCs while sparing normal HSPCs. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and suppresses the PBX3-mediated leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy in AML.
2026-04-28 | GSE329270 | GEO
Project description:RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication
2022-08-16 | MSV000090142 | MassIVE
Project description: Not available
| S-EPMC5564591 | biostudies-literature
Project description: Not available
| S-EPMC7849765 | biostudies-literature
Project description: Not available
| S-EPMC4127019 | biostudies-literature