Dokumentenart: | Artikel | ||||||
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Titel eines Journals oder einer Zeitschrift: | Blood | ||||||
Verlag: | American Society of Hematology, HighWire Press, | ||||||
Band: | 110 | ||||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 4 | ||||||
Seitenbereich: | S. 1291-1300 | ||||||
Datum: | 15 August 2007 | ||||||
Institutionen: | Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatik und Data Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||
Identifikationsnummer: |
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Stichwörter / Keywords: | "Adult", "Aged", "Chromosome Aberrations", "Chromosome Inversion", "Cluster Analysis", "Core Binding Factors", "Female", "Gene Expression Profiling", "Gene Expression Regulation, Neoplastic", "Humans", "Karyotyping", "Leukemia, Myeloid, Acute", "Male", "Middle Aged", "Mutation", "Oligonucleotide Array Sequence Analysis", "Prognosis", "Proto-Oncogene Proteins c-kit", "Survival Rate", "Tumor Markers, Biological", "fms-Like Tyrosine Kinase 3" | ||||||
Dewey-Dezimal-Klassifikation: | 000 Informatik, Informationswissenschaft, allgemeine Werke > 004 Informatik 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||||
Status: | Veröffentlicht | ||||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||||
An der Universität Regensburg entstanden: | Zum Teil | ||||||
Dokumenten-ID: | 32957 |
Zusammenfassung
Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biologic and clinical heterogeneity within these cytogenetic groups that is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene ...
Zusammenfassung
Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biologic and clinical heterogeneity within these cytogenetic groups that is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n = 93) of AML patients with CBF leukemia (inv (16), n = 55; t(8;21), n = 38). By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n = 35) characterized by shorter overall survival times (P = .03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21) subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P = .011 and P = .026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the ``favorable'' CBF leukemias, antiapoptotic mechanisms and deregulated mTOR signaling and, in the newly defined ``unfavorable'' subgroup, aberrant MAPK signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biologic basis for the heterogeneity observed in CBF leukemia.
Metadaten zuletzt geändert: 29 Sep 2021 07:40