Nucleophosmin 1 lactylation in graft kidney induces ferroptotic trigger waves that exacerbate delayed graft function [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE306588 | GEO | 2025/11/05
REPOSITORIES: GEO
Similar Datasets
Project description:To identify the genome-wide binding sites of lactylated NPM1 and understand its role in transcriptional regulation.
2025-11-05 | GSE306531 | GEO
Project description:Nucleophosmin 1 lactylation in graft kidney induces ferroptotic trigger waves that exacerbate delayed graft function
| PRJNA1311076 | ENA
Project description:Nucleophosmin 1 lactylation in graft kidney induces ferroptotic trigger waves that exacerbate delayed graft function [RNA-Seq]
| PRJNA1311357 | ENA
Project description:Multilineage dysplasia (MLD) has no impact on biological, clinico-pathological and prognostic features of AML with mutated nucleophosmin (NPM1) NPM1-mutated AML is a provisional entity in the WHO-2008 classification of myeloid neoplasms. The significance of concomitant multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the WHO-2008 classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia(MD)-related changes. We evaluated the MLD impact in 378 NPM1-mutated AML patients. MLD was found in about 25% cases. Except for a lower WBC and FLT3-ITD incidence in MLD+ group, no significant differences were observed in age, sex, cytogenetics and FLT3-TKD between NPM1-mutated AML with and without MLD. Notably, NPM1-mutated AML with/without MLD showed overlapping immunophenotype (CD34-negativity) and GEP (CD34 downregulation and HOX genes upregulation). Moreover, OS and EFS did not differ among NPM1-mutated AML patients, independently of whether they carried or not MLD, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the most significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML should be considered as one disease entity clearly distinct from AML with MD-related changes. These findings have important diagnostic and prognostic implications in AML. All bone marrow samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation. 48 samples
2010-07-30 | E-GEOD-18018 | biostudies-arrayexpress
Project description:Multilineage dysplasia (MLD) has no impact on biological, clinico-pathological and prognostic features of AML with mutated nucleophosmin (NPM1) NPM1-mutated AML is a provisional entity in the WHO-2008 classification of myeloid neoplasms. The significance of concomitant multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the WHO-2008 classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia(MD)-related changes. We evaluated the MLD impact in 378 NPM1-mutated AML patients. MLD was found in about 25% cases. Except for a lower WBC and FLT3-ITD incidence in MLD+ group, no significant differences were observed in age, sex, cytogenetics and FLT3-TKD between NPM1-mutated AML with and without MLD. Notably, NPM1-mutated AML with/without MLD showed overlapping immunophenotype (CD34-negativity) and GEP (CD34 downregulation and HOX genes upregulation). Moreover, OS and EFS did not differ among NPM1-mutated AML patients, independently of whether they carried or not MLD, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the most significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML should be considered as one disease entity clearly distinct from AML with MD-related changes. These findings have important diagnostic and prognostic implications in AML.
2010-07-01 | GSE18018 | GEO
Project description:Nucleophosmin (NPM1), a nucleolar protein frequently mutated in haematopoietic malignancies, is overexpressed in several solid tumours with poorly understood functional roles. Here, we demonstrate that Npm1 is upregulated following APC loss in WNT-responsive tissues and supports WNT-driven intestinal and liver tumourigenesis. Mechanistically, NPM1 loss induces ribosome pausing and accumulation at the 5’-end of coding sequences, triggering a protein synthesis stress response and p53 activation, which mediate this anti-tumourigenic effect. Collectively, our data identify NPM1 as a critical WNT effector that sustains WNT-driven hyperproliferation and tumourigenesis by attenuating the integrated stress response (ISR) and p53 activation. Notably, NPM1 expression correlates with elevated WNT signalling and proliferation in human colorectal cancer (CRC), while CRCs harbouring NPM1 deletions exhibit preferential TP53 inactivation, underscoring the clinical relevance of our findings. Being dispensable for adult epithelial homeostasis, NPM1 represents a promising therapeutic target in p53-proficient WNT-driven tumours, including treatment-refractory KRAS-mutant CRC, and hepatic cancers.
2025-09-29 | GSE309379 | GEO
Project description:Nucleophosmin (NPM1) is a nucleolar protein frequently mutated in haematopoietic malignancies and overexpressed in many solid tumours, but little is known about its functional role in carcinogenesis. Here, we identify NPM1 as a commonly upregulated gene following APC loss in tissues that positively respond to high WNT signalling. High NPM1 expression correlates with increased proliferation in patients with colorectal cancer (CRC). We show that whilst dispensable for adult epithelial tissue homeostasis, NPM1 loss has a profound effect on WNT-driven intestinal and liver tumourigenesis, leading to reduced proliferation and extension of survival. Mechanistically, NPM1 depletion triggers integrated stress response (ISR) and p53 pathway activation. Genetically or chemically blunting these pathways, rescues proliferation following NPM1 loss. Overall, our results demonstrate that NPM1 supports WNT-driven cell proliferation and tumour initiation by attenuating induction of ISR and p53 pathway activation. Being dispensable for homeostasis, NPM1 presents itself as a promising target for cancer therapy in WNT-driven tumours with functional p53, including treatment-refractory KRAS-mutant CRC and hepatic cancers.
2025-08-12 | PXD062969 | Pride
Project description:NPM1 is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Concurrent inflammatory bowel diseases (IBD) and MDS have been reported frequently, indicating a close relationship between IBD and MDS. Here, we examined the role of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 was reduced in IBD patients. Npm1+/- mice were more susceptible to acute colitis and experimentally induced CAC than littermate controls. Npm1 deficiency impaired the function of IL-22-producing group 3 innate lymphoid cells (ILC3s). Mice lacking Npm1 in ILC3s exhibited decreased IL-22 production and accelerated development of colitis. NPM1 was important for mitochondrial biogenesis and metabolism by oxidative phosphorylation in ILC3s. Further experiments revealed that NPM1 cooperates with p65 to promote TFAM transcription in ILC3s. Overexpression of Npm1 in mice enhanced ILC3 function and reduced severity of DSS-induced colitis. Thus, our findings suggest the protective function of NPM1 in ILC3s against IBD by regulating mitochondrial metabolism through p65-TFAM axis.
2024-07-09 | GSE271455 | GEO
Project description:Nucleophosmin (NPM1) is a nucleolar protein frequently overexpressed in many solid tumours with little known about its functional role to support carcinogenesis. Here, we identify Npm1 as a commonly upregulated gene following Apc loss in highly proliferative tissues, and high expression correlates with increased proliferation in CRC patients. We show that NPM1 is dispensable for adult epithelial tissue homeostasis, however, it has a profound effect on WNT-driven intestinal and liver tumourigenesis, leading to reduced proliferation and extension of survival. Mechanistically, NPM1 depletion triggers integrated stress response (ISR) and p53 pathway activation. P53 deletion, or inhibition of the ISR effects, rescue proliferation following NPM1 loss. Overall, our results demonstrate that NPM1 supports WNT-driven cell proliferation and tumour initiation by attenuating p53 pathway activation or induction of ISR. Being dispensable for homeostasis, NPM1 presents as a promising target for cancer therapy in WNT-driven tumours with functional p53, including difficult to treat KRAS-mutant CRC and hepatic cancers.
2024-02-15 | GSE249958 | GEO
Project description:Gene expression in NPM1 wildtype and mutated AML patients with high or low hsa_circ_0075001 expression In acute myeloid leukemia there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wildtype and mutated acute myeloid leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and acute myeloid leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as acute myeloid leukemia subgroup-specific circRNA signatures.
2017-09-22 | GSE104099 | GEO