The role of the leukemia-associated ETO homologue repressors in hematopoiesis

André Olsson

Research output: ThesisDoctoral Thesis (compilation)

58 Downloads (Pure)

Abstract

The fusion protein AML1-ETO is observed in acute myeloid patients with the chromosomal translocation t(8;21). Cells with this chimeric protein have impaired granulocytic and erythroid differentiation with accumulation of myeloblasts. The transcriptional co-repressor ETO (Eight Twenty One) was identified from the cloning of AML1-ETO. Subsequently, MTGR1 (Myeloid Translocation Gene-Related protein 1) and MTG16 (Myeloid Translocation Gene on chromosome 16) were found to be homologues to ETO, all these proteins being transcriptional co-repressors present in complexes together with other co-repressors such as SIN3, N-CoR and SMRT, and histone deacetylases. The objective of this thesis was to investigate the role of the ETO-homologues in hematopoiesis and leukemia. First, the finding of physical interactions between ETO homologues suggested a possible cooperation. Second, a ubiquitous expression was observed for MTGR1 and MTG16 in hematopoietic lineages. We also discovered that the expression of ETO was restricted to the erythroid lineage suggesting a role for ETO in erythroid development. Furthermore, we found that MTG16 was downregulated during erythroid and granulocytic differentiation, which also implements a role for MTG16 in the regulation of hematopoietic differentiation. Additionally, cells expressing AML1-ETO showed downregulation of MTG16, which possibly can contribute to the impaired differentiation of these cells. Finally, we studied the transcriptional repression of the ETO-homologues in a reporter gene system. MTG16 was found to be a potent co-repressor. Despite a physical interaction, the co-repressors N-CoR and hSIN3B did not augment MTG16-mediated repression. Collectively, our data suggests that the ETO homologues may have differential roles in the regulation of hematopoietic differentiation.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Division of Hematology and Transfusion Medicine
Supervisors/Advisors
  • Olsson, Inge, Supervisor
Award date2006 Nov 3
Publisher
Print ISBNs91-85559-49-0
Publication statusPublished - 2006

Bibliographical note

Defence details

Date: 2006-11-03
Time: 09:00
Place: Segerfalksalen, Wallenberg Neurocentrum, BMC, Sölvegatan 17, Lund

External reviewer(s)

Name: Öberg, Fredrik
Title: Docent
Affiliation: Uppsala Universitet

---


<div class="article_info">SR Lindberg, A Olsson, A-M Persson and I Olsson. <span class="article_issue_date">2003</span>. <span class="article_title">Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins.</span> <span class="journal_series_title">Eur J Haematol</span>, <span class="journal_volume">vol 71</span> <span class="journal_pages">pp 439-47</span>.</div>
<div class="article_info">SR Lindberg, A Olsson, A-M Persson and I Olsson. <span class="article_issue_date">2005</span>. <span class="article_title">The Leukemia Associated ETO Homologues Are Differently Expressed During Hematopoietic Differentiation.</span> <span class="journal_series_title">Experimental Hematology</span>, <span class="journal_volume">vol 33</span> <span class="journal_pages">pp 189-98</span>.</div>
<div class="article_info">A Olsson, I Olsson and RS Dhanda. <span class="article_issue_date"></span>. <span class="article_title">Transcriptional repression by the leukaemia-associated ETO-homologue MTG16 and the interacting co-repressors SIN3B and N-CoR.</span> (submitted)</div>
<div class="article_info">A Olsson, SR Lindberg, I Olsson and J Mulloy. <span class="article_issue_date"></span>. <span class="article_title">AML1-ETO inhibits expression of the leukemia associated ETO-homologue repressor protein MTG16.</span> (manuscript)</div>

Subject classification (UKÄ)

  • Hematology

Keywords

  • MTGR1
  • ETO
  • MTG16
  • AML1-ETO
  • hematopoiesis
  • leukemia
  • diffferentiation
  • extracellular fluids
  • Haematology
  • Medicin (människa och djur)
  • extracellulära vätskor
  • Hematologi
  • Medicine (human and vertebrates)

Fingerprint

Dive into the research topics of 'The role of the leukemia-associated ETO homologue repressors in hematopoiesis'. Together they form a unique fingerprint.

Cite this