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ROLE PATHOLOGIQUE DES ANOMALIES DE L'HETEROCHROMATINE PERICENTROMERIQUE DU CHROMOSOME 1 DANS LES LYMPHOMES B MALINS NON-HODGKINIENS

Abstract : Chromosomal rearrangements targeting human chromosome 1 constitutive heterochromatin region (cytogenetic band 1q12) are remarkably frequent in lymphoma, myeloma, acute leukaemia and in some solid tumours. This highly suggests existence of constitutive heterochromatin-dependent oncogenic mechanisms in these diseases. My PhD works show that these rearrangements induce profound alterations of chromatin organisation and function in lymphoma B-cells. Major consequences are the formation of aberrant heterochromatic foci resulting from long range intra-chromosomal ‘matching' between the rearranged 1q12 and centromeric regions. These foci are associated with an enrichment of adjacent euchromatic sequences in repressive epigenetic marks, and with deregulated expression of genes such as GMCL1 and MXD1 which encodes proteins involved in the control of P53 and MYC pathways, respectively. In the other hand, a pilot study of transcriptional profiling by Affymetrix arrays in cases of human lymphoma with or without 1q12 heterochromatin rearrangement confirms and identifies new targets for deregulation linked to heterochromatin in non-Hodgkin B-cell lymphoma. Understanding the role of these aberrant heterochromatic foci would be of major interest for haematological and solid tumours, since these anomalies are frequent and non-random in a large panel of human tumours, and are associated to tumour progression and poor prognosis.
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https://tel.archives-ouvertes.fr/tel-00545209
Contributor : Alexandra Fournier <>
Submitted on : Thursday, December 9, 2010 - 6:04:50 PM
Last modification on : Friday, November 6, 2020 - 4:02:41 AM
Long-term archiving on: : Thursday, March 10, 2011 - 2:01:59 PM

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  • HAL Id : tel-00545209, version 1

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U823 | UJF | UGA

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Alexandra Fournier. ROLE PATHOLOGIQUE DES ANOMALIES DE L'HETEROCHROMATINE PERICENTROMERIQUE DU CHROMOSOME 1 DANS LES LYMPHOMES B MALINS NON-HODGKINIENS. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00545209⟩

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