Human Gene Set: MULLIGHAN_NPM1_MUTATED_SIGNATURE_2_UP


Standard name MULLIGHAN_NPM1_MUTATED_SIGNATURE_2_UP
Systematic name M6590
Brief description The 'NPM1-mutated signature 2': genes up-regulated in pediatric AML (acute myeloid leukemia) samples with mutated NPM1 [GeneID=4869] compared to the AML cases with the intact gene and without recurring cytogenetic anomalities or M7 phenotype.
Full description or abstract Somatic mutations in nucleophosmin (NPM1) occur in approximately 35% of adult acute myeloid leukemia (AML). To assess the frequency of NPM1 mutations in pediatric AML, we sequenced NPM1 in the diagnostic blasts from 93 pediatric AML patients. Six cases harbored NPM1 mutations, with each case lacking common cytogenetic abnormalities. To explore the phenotype of the AMLs with NPM1 mutations, gene expression profiles were obtained using Affymetrix U133A microarrays. NPM1 mutations were associated with increased expression of multiple homeobox genes including HOXA9, A10, B2, B6 and MEIS1. As dysregulated homeobox gene expression is also a feature of MLL-rearranged leukemia, the gene expression signatures of NPM1-mutated and MLL-rearranged leukemias were compared. Significant differences were identified between these leukemia subtypes including the expression of different HOX genes, with NPM1-mutated AML showing higher levels of expression of HOXB2, B3, B6 and D4. These results confirm recent reports of perturbed HOX expression in NPM1-mutated adult AML, and provide the first evidence that the NPM1-mutated signature is distinct from MLL-rearranged AML. These findings suggest that mutated NPM1 leads to dysregulated HOX expression via a different mechanism than MLL rearrangement.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17597811   Authors: Mullighan CG,Kennedy A,Zhou X,Radtke I,Phillips LA,Shurtleff SA,Downing JR
Exact source Table 3S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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