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Distinct gene expression patterns associated with FLT3- and NRAS-activating mutations in acute myeloid leukemia with normal karyotype.
Oncogene. 2005 Feb 24; 24(9):1580-8.O

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.

Authors+Show Affiliations

Division of Molecular Genetics (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15674343

Citation

Neben, Kai, et al. "Distinct Gene Expression Patterns Associated With FLT3- and NRAS-activating Mutations in Acute Myeloid Leukemia With Normal Karyotype." Oncogene, vol. 24, no. 9, 2005, pp. 1580-8.
Neben K, Schnittger S, Brors B, et al. Distinct gene expression patterns associated with FLT3- and NRAS-activating mutations in acute myeloid leukemia with normal karyotype. Oncogene. 2005;24(9):1580-8.
Neben, K., Schnittger, S., Brors, B., Tews, B., Kokocinski, F., Haferlach, T., Müller, J., Hahn, M., Hiddemann, W., Eils, R., Lichter, P., & Schoch, C. (2005). Distinct gene expression patterns associated with FLT3- and NRAS-activating mutations in acute myeloid leukemia with normal karyotype. Oncogene, 24(9), 1580-8.
Neben K, et al. Distinct Gene Expression Patterns Associated With FLT3- and NRAS-activating Mutations in Acute Myeloid Leukemia With Normal Karyotype. Oncogene. 2005 Feb 24;24(9):1580-8. PubMed PMID: 15674343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct gene expression patterns associated with FLT3- and NRAS-activating mutations in acute myeloid leukemia with normal karyotype. AU - Neben,Kai, AU - Schnittger,Susanne, AU - Brors,Benedikt, AU - Tews,Björn, AU - Kokocinski,Felix, AU - Haferlach,Torsten, AU - Müller,Jasmin, AU - Hahn,Meinhard, AU - Hiddemann,Wolfgang, AU - Eils,Roland, AU - Lichter,Peter, AU - Schoch,Claudia, PY - 2005/1/28/pubmed PY - 2005/3/23/medline PY - 2005/1/28/entrez SP - 1580 EP - 8 JF - Oncogene JO - Oncogene VL - 24 IS - 9 N2 - 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. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/15674343/Distinct_gene_expression_patterns_associated_with_FLT3__and_NRAS_activating_mutations_in_acute_myeloid_leukemia_with_normal_karyotype_ L2 - https://doi.org/10.1038/sj.onc.1208344 DB - PRIME DP - Unbound Medicine ER -