[Mechanisms of leucemogenesis].
The genetic origins of the development of malignant haematological disorders have been established at the beginning of the 80ies. Systematic characterization of chromosomal structural abnormalities and, more recently by DNA microarray approaches and sequencing of tumour genomes have allowed the identification of a large number of genes that are mutated during malignant transformation in humans. Functional studies of these human oncogenes have shown that most of them were not able to transform a haematologic progenitor when acting alone and that cooperation with other oncogenic events was required. The present challenges are the evaluation of the role of each mutation in malignant transformation and the definition of the chronology of their emergence. From these data, the development of efficient therapeutic approaches will be possible by targeting the early oncogenic events which are at the origin of the malignant transformation.
Inserm U985, Institut Gustave-Roussy, Villejuif, France. olivier.bernard@inserm.fr
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D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D050658:Core Binding Factor beta Subunit / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics; D050939:Gene Fusion / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein
C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C488373:TEL-RUNX1 fusion protein, human; D000090243:Nucleophosmin; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase