RGD Reference Report - Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice.

Authors: Vassiliou, GS  Cooper, JL  Rad, R  Li, J  Rice, S  Uren, A  Rad, L  Ellis, P  Andrews, R  Banerjee, R  Grove, C  Wang, W  Liu, P  Wright, P  Arends, M  Bradley, A 
Citation: Vassiliou GS, etal., Nat Genet. 2011 May;43(5):470-5. doi: 10.1038/ng.796. Epub 2011 Mar 27.
RGD ID: 11534990
Pubmed: PMID:21441929   (View Abstract at PubMed)
PMCID: PMC3084174   (View Article at PubMed Central)
DOI: DOI:10.1038/ng.796   (Journal Full-text)

Acute myeloid leukemia (AML) is a molecularly diverse malignancy with a poor prognosis whose largest subgroup is characterized by somatic mutations in NPM1, which encodes nucleophosmin. These mutations, termed NPM1c, result in cytoplasmic dislocation of nucleophosmin and are associated with distinctive transcriptional signatures, yet their role in leukemogenesis remains obscure. Here we report that activation of a humanized Npm1c knock-in allele in mouse hemopoietic stem cells causes Hox gene overexpression, enhanced self renewal and expanded myelopoiesis. One third of mice developed delayed-onset AML, suggesting a requirement for cooperating mutations. We identified such mutations using a Sleeping Beauty transposon, which caused rapid-onset AML in 80% of mice with Npm1c, associated with mutually exclusive integrations in Csf2, Flt3 or Rasgrp1 in 55 of 70 leukemias. We also identified recurrent integrations in known and newly discovered leukemia genes including Nf1, Bach2, Dleu2 and Nup98. Our results provide new pathogenetic insights and identify possible therapeutic targets in NPM1c+ AML.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NPM1Humanacute myeloid leukemia onsetISONpm1 (Mus musculus) RGD 
Npm1Ratacute myeloid leukemia onsetISONpm1 (Mus musculus) RGD 
Npm1Mouseacute myeloid leukemia onsetIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Npm1  (nucleophosmin 1)

Genes (Mus musculus)
Npm1  (nucleophosmin 1)

Genes (Homo sapiens)
NPM1  (nucleophosmin 1)


Additional Information