| Item type: | Article | ||||||
|---|---|---|---|---|---|---|---|
| Journal or Publication Title: | Blood | ||||||
| Publisher: | American Society of Hematology, HighWire Press, | ||||||
| Volume: | 110 | ||||||
| Number of Issue or Book Chapter: | 4 | ||||||
| Page Range: | pp. 1291-1300 | ||||||
| Date: | 15 August 2007 | ||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatics and Data Science > Department Computational Life Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||
| Identification Number: |
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| 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 Decimal Classification: | 000 Computer science, information & general works > 004 Computer science 600 Technology > 610 Medical sciences Medicine | ||||||
| Status: | Published | ||||||
| Refereed: | Yes, this version has been refereed | ||||||
| Created at the University of Regensburg: | Partially | ||||||
| Item ID: | 32957 |
Abstract
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 ...
Abstract
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.
Metadata last modified: 29 Sep 2021 07:40
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