Epigenetic-based treatments emphasize the biologic differences of core-binding factor acute myeloid leukemias
Autor: | Vanesa Orantes, Adriana Lasa, Elena Serrano, Anna Aventin, Maria J. Carnicer, Salut Brunet, Jorge Sierra, Josep F. Nomdedeu, Jorge Pena |
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Rok vydání: | 2008 |
Předmět: |
Adult
Cancer Research Myeloid Oncogene Proteins Fusion Chromosomes Human Pair 21 Decitabine Biology Hydroxamic Acids Translocation Genetic Chromatin remodeling Leukemogenic Epigenesis Genetic Fusion gene RUNX1 Translocation Partner 1 Protein hemic and lymphatic diseases Biomarkers Tumor Tumor Cells Cultured medicine Humans RNA Messenger Enzyme Inhibitors Promoter Regions Genetic DNA Modification Methylases Oligonucleotide Array Sequence Analysis Regulation of gene expression Gene Expression Regulation Leukemic Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Myeloid leukemia U937 Cells Hematology DNA Methylation Chromatin Assembly and Disassembly medicine.disease Molecular biology Histone Deacetylase Inhibitors Leukemia Myeloid Acute Leukemia medicine.anatomical_structure Oncology Chromosome Inversion Core Binding Factor Alpha 2 Subunit Mutation Azacitidine Chromosomes Human Pair 16 Chromosomes Human Pair 8 medicine.drug |
Zdroj: | Leukemia Research. 32:944-953 |
ISSN: | 0145-2126 |
Popis: | Acute myeloid leukemia (AML) is a heterogeneous group of disorders characterized by an abnormal proliferation of the myeloid precursors and a maturation block. The most common chromosomal lesions in AML are the t(8;21) and inv(16). To better understand the leukemogenic mechanism of these fusion proteins, we performed gene expression studies in samples from (8;21), AML1 mutated and inv(16) patients, as well as from the Kasumi-1 cell line and a U937 cell line expressing the AML1-ETO fusion gene. To assess the influence of associated epigenetic lesions, we performed gene expression studies in Kasumi-1 cells and cells extracted from an Inv(16) patient, both treated with demethylating and HDAC inhibitor agents. Shared deregulated genes in the different types of core-binding factor leukemias were identified. We found a tight link between Inv(16) and mutant AML1 samples. Furthermore, some of the genes deregulated by the leukemogenic process reverted to their normal expression with demethylating and HDAC inhibitor treatment, highlighting the role of chromatin remodeling processes in AML. |
Databáze: | OpenAIRE |
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