Systematic name M17856
Brief description The 'MLL signature 1': genes up-regulated in pediatric AML (acute myeloid leukemia) with rearranged MLL [GeneID=4297] compared to all AML cases with the intact gene.
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 gene sets
      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 5S
Related gene sets (show 9 additional gene sets from the source publication)

(show 34 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (Broad Institute)
Source platform HG-U133A
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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