Dr. Anne Dejean

International Awards

Hamdan Award for Medical Research Excellence - Therapy in Leukemia
1999-2000
Dr. Anne Dejean is Directeur de Recherche de l'INSERM at the prestigious Pasteur Institute in Paris, France. She obtained her doctoral degree at the University of Paris and is affiliated with Pasteur Institute from 1980. She is corresponding member of French Academy of Science and winner of several research awards for her research achievements.
Dr Anne Dejean and her group were at the origin of the discovery of the relationship between rearrangements of the retinoic acid receptor genes and human cancers. Studying the molecular basis of HBV¬associated hepatocellularcarcinoma with Prof. Pierre Tiollais, she was the first to demonstrate that the viral DNA can be integrated in unique sites into the human genome.
 
Studies of these sites revealed that the viral coding sequences were linked to a member of the steroid/vitamin hormone receptor super family. Together with Prof. Pierre Chambon's laboratory, she showed that this new gene was in fact one of the receptors for retinoic acid (RARb). Then, she could demonstrate that the fusion HBV-RARb protein is indeed oncogenic.
 
The demonstration that a retinoic acid receptor can be modified in tumors prompted her collaboration with prof. Laurent Degos in the study of acute promyelocytic leukemia (APL) characterized by a specific t( 15; 17) chromosomal translocation. In a brilliant series of papers, she showed that an as yet unknown gene named PML is fused to the retinoic acid receptor (RARa) in this case. A similar observation was made shortly after by two other American and European groups. This observation is of extreme clinical interest since retinoic acid induces complete remissions in patients suffering from acute promyelocytic leukaemia by inducing the differentiation of the leukemic blasts into mature granulocytes. More recent work of Anne Dejean brings clues for the therapeutic effect of retinoic acid in this disease. In fact, she discovered that PML is a component of a novel type of subnuclear structures, the so-called PML nuclear bodies, which are entirely disrupted in the leukemic APL cell nuclei. Strikingly, retinoic acid treatment induces the complete re-organisation of these nuclear bodies, thus correlating with cell differentiation and remissions in the patients.
 
These results strongly support the hypothesis that the beneficial role of retinoic acid in promoting myeloid cell differentiation in APL is directly linked to its ability to restore a normal subnuclear organisation. In this context, considerable effort is now devoted to the elaboration of more potent synthetic retinoids. Studying the molecular basis for the acquired resistance to retinoic acid which can be observed in a subset of APL patients, her group and two other groups recently discovered a change in the regulation of the chromatin structure in these patients. These results have kindled the hope to develop new therapeutic approaches through the use of chromatin remodelling drugs such as histone deacetylase inhibitors which have already proved to be efficient in preliminary clinical trials. In conclusion, the work of Anne Dejean and her colleagues has greatly advanced our understanding of the genetic defects involved in human leukemogenesis, it has revealed new aspects of cellular differentiation and has opened new avenues in our improvement of treatment strategies for human leukemia.
 
Therefore, she gained international recognition as one of the leading scientists in the field of hormone receptors, differentiation therapy and leukemia.
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