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
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