Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539821
Title: Involvement of ID4 (Inhibitor of DNA Binding 4) in haematopoietic malignancies
Author: Dusanjh, Palminder Kaur
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2011
Availability of Full Text:
Access through EThOS:
Access through Institution:
Abstract:
Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus have been described in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). One of these, t (6;14)(p22;q32), involved the Inhibitor of DNA Binding 4 (ID4) gene, resulting in deregulated ID4 expression. Members of the ID family are helix-loop-helix proteins that lack DNA binding domains. They are thought to regulate cellular differentiation and proliferation by binding and sequestering E proteins from their DNA targets. The aim of this thesis was to examine the expression and oncogenic potential of ID4 in B-cells. ID4 expression was detected in a subset of chronic lymphocytic leukaemia (CLL) and BCP-ALL lacking the ID4/IGH chromosomal translocation. ID4 expression defined a subtype of BCP-ALL with a distinctive gene signature. ID4, unlike other members of the ID family is not expressed in normal B-cells. Unexpectedly, ectopic ID4 protein expression in most but not all derived B-cell lines reduced proliferation and induced cell cycle arrest. B-cells in ID4-induced cell cycle arrest showed a partial resistance to apoptosis. Proteomic analysis of cell lines expressing ectopic ID4 showed that ID4 interacted with E proteins, although these data could not be confirmed with endogenous ID4 for technical reasons. Primary normal mouse B lymphocyte progenitors showed impaired B-cell development in an in vitro assay following expression of ID4. In contrast, ID4 cooperated with myc over-expression in inducing proliferation of murine B lymphocyte progenitors. Collectively, these data suggest that ID4 may be a novel genetic “driver” in different subtypes of B-cell malignancy. ID4 may contribute to leukemogenesis of B-cell progenitors by inducing inappropriate gene expression and affecting mitosis. This collectively promotes genetic instability and generates a preleukemic stage.
Supervisor: Dyer, Martin ; Karran, Elizabeth Sponsor: Not available
Qualification Name: Not available Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.539821  DOI: Not available
Share: