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Theses

Mise en évidence de régions minimales critiques par CGH array haute résolution de leucémies aiguës myéloblastiques induites par les traitements anti-néoplasiques (t-LAM) et de leucémies aiguës myéloblastiques de novo (p-LAM)

Abstract : The antineoplastic treatments can have consequences such as therapy-related leukaemia (t-AML). These t-AML presents specific chromosomal abnormalities following the mutagenic agent. Monosomies 5 or 7 or 5q-/7q-meets after alkylatig agent exposures; balanced translocations often involving11q23.3, after anti topoisomérases II. These acquired abnormalities are also common to de novo acute myeloblastic leukemia ( p-LAM ) suggesting similar leucemogenic mechanisms between t-LAM and p-LAM. The use of the high-resolution CGH array allows bringing to light cryptic abnormalities. 36 patients presenting a t-AML and 49 affected by a p-LAM have been studied with this tool. The purpose is to look for CNA (Copy Number Abnormalities) within t-LAM and p-LAM. Some of these CNA were able to be grouped together in minimal critical region (MCR) which can contain candidate genes in the induced and\or primitive leukemogenesis. These results were compared with already published data. RMC localized in 5q and 7q stay still too big to define easily candidate genes. In other regions, RUNX1, NF1, ETS2 or TET2 are brought to light with different frequencies between t-LAM and p-LAM. A classification of the acquired genomic abnormalities of LAM in 3 groups is proposed: the abnormalities common to t-LAM and to p-LAM, the abnormalities essentially found in t-LAM or in p-LAM. The study of the transcriptome and the miRNome concerned a small number of patients studied in CGH array. The interpretation of the preliminary results remains difficult when they are compared with the genomic data.
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  • HAL Id : tel-00831321, version 1

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Nathalie Itzhar Baïkian. Mise en évidence de régions minimales critiques par CGH array haute résolution de leucémies aiguës myéloblastiques induites par les traitements anti-néoplasiques (t-LAM) et de leucémies aiguës myéloblastiques de novo (p-LAM). Génétique. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66212⟩. ⟨tel-00831321⟩

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