Aspects biologiques et génétiques des leucémies aigues Implication des gènes FLT3 et NPM1 dans la réponse au traitement.

Abstract

Leukemia is a very heterogeneous group of malignant homeopathies and this heterogeneousness expresses itself more particularly in the acute leukemia where sometimes it turns out to be difficult to make the distinction between the various entities. The physiopathology of this disease is starting to be understood at the cellular and molecular levels, and cytogenetic markers have become the most important for the stratification of the risk and the treatment of the patients. However, with the advent of the new technologies, the identification of other molecular markers, like gene mutations and the characterization of the profiles of the epigenetic modifications, began to play an important role in the understanding of the disease. The identification of these biomarkers contributes to a better understanding and a better treatment strategies of the patients. At first of our work, we proceeded to a transverse study on the acute leukaemia, and for that we made a hematological, cytological and cytogenetic analysis for acute leukemia patients who were received at hematology center in our hospital. Secondly, molecular variations of the gene FLT3 (FLT3-ITD and FLT3-TKD) and of the exon12 of the gene NPM1 were analysed for the AML patients. Our results reveal that FLT3 and NPM1 mutations are less frequent in our population than reported in literature. we were also able to describe a new unreported complex mutation in the exon 12 of the NPM1 gene. Finally, we analyzed the effect of the presence of the previously detected mutations on the answer to the treatment, the survival and the future of the AML patients. Our results showed that the mutations of the FLT3 have a pejorative effect on the future of the patients, they indeed increase, the possibility relapse and death rate contrary to the mutations of the NPM1 gene which appear to have a positive effect on the AML patients when they are not associated with the FLT3-ITDs. The molecular and cytogenetic analysis for leukemia patients’ turned out to be an important diagnosis tool for prognosis of the acute leukemia. The specific association between acute leukemia subtypes and certain anomalies was clearly established. These analyses are important for confirming the diagnosis, to establish a prognosis, to make a choice and a therapeutic follow-up and consequently, the management of patients at the hematological centers can be improved.