Human Gene Set: NEBEN_AML_WITH_FLT3_OR_NRAS_DN


Standard name NEBEN_AML_WITH_FLT3_OR_NRAS_DN
Systematic name M12530
Brief description Genes down-regulated in acute myeloid leukemia (AML) samples with constitutively activated FLT3 [GeneID=2322] or with activating point mutations within NRAS [GeneID=4893].
Full description or abstract In acute myeloid leukemia (AML), constitutive activation of the FLT3 receptor tyrosine kinase, either by internal tandem duplications (FLT3-ITD) of the juxtamembrane region or by point mutations in the second tyrosine kinase domain (FLT3-TKD), as well as point mutations of the NRAS gene (NRAS-PM) are among the most frequent somatic gene mutations. To elucidate whether these mutations cause aberrant signal transduction in AML, we used gene expression profiling in a series of 110 newly diagnosed AML patients with normal karyotype. The different algorithms used for data analysis revealed highly concordant sets of genes, indicating that the identified gene signatures are specific for each analysed subgroup. Whereas samples with FLT3-ITD and FLT3-TKD could be separated with up to 100% accuracy, this did not apply for NRAS-PM and wild-type samples, suggesting that only FLT3-ITD and FLT3-TKD are associated with an apparent signature in AML. The set of discriminating genes included several known genes, which are involved in cell cycle control (CDC14A, WEE1), gene transcription (HOXB5, FOXA1), and signal transduction (SMG1). In conclusion, we showed that unique gene expression patterns can be correlated with FLT3-ITD and FLT3-TKD. This might lead to the identification of further pathogenetic relevant candidate genes particularly in AML with normal karyotype.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15674343   Authors: Neben K,Schnittger S,Brors B,Tews B,Kokocinski F,Haferlach T,Müller J,Hahn M,Hiddemann W,Eils R,Lichter P,Schoch C
Exact source Table 2: Fold change < -2
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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