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Transcriptional regulation and effects on differentiation by LMO proteins and the basic helix-loop-helix factors TAL1 and HEN1

Hansson, Anders LU (2004)
Abstract
Acute lymphoblastic leukemia (ALL) is the most widespread type of cancer, as well as the most frequent leukemia in children. Malignant ALL cells originate from normal T lymphocytes or B cells that are blocked at immature stages of differentiation. Since T cell lineage derived ALL in children is associated with various unfavorable features, it is no surprise that childhood T lineage ALL have been reported to have a worse prognosis than childhood B lineage ALL. However, the development of new diagnostic and therapeutic strategies have, in recent years improved the outcome for children with T cell ALL. Yet, the molecular basis of pathogenesis remains largely unknown. A number of transcription factors involved in normal blood cell development,... (More)
Acute lymphoblastic leukemia (ALL) is the most widespread type of cancer, as well as the most frequent leukemia in children. Malignant ALL cells originate from normal T lymphocytes or B cells that are blocked at immature stages of differentiation. Since T cell lineage derived ALL in children is associated with various unfavorable features, it is no surprise that childhood T lineage ALL have been reported to have a worse prognosis than childhood B lineage ALL. However, the development of new diagnostic and therapeutic strategies have, in recent years improved the outcome for children with T cell ALL. Yet, the molecular basis of pathogenesis remains largely unknown. A number of transcription factors involved in normal blood cell development, have been shown to induce T cell malignancies when aberrantly expressed in T cells. However, the mechanisms by which these proteins contribute to tumorigenesis are essentially undefined. This study has focused on the normal and oncogenic pathways of two such transcription factors, termed LMO2 and TAL1, both crucial for normal blood development as well as implicated in the genesis of a subset of T cell leukemias. We have also investigated the functions of LMO2 and TAL1 related proteins. Here we show that the pTa and p16 genes are potential target genes for TAL1, indicating that TAL1 might interfere with both differentiation and cell cycle control. Thus, suggesting that TAL1 might possess dual tumorigenic qualities. Moreover, we demonstrate that LMO2 is involved in erythropoiesis. (Less)
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author
opponent
  • Dr Grandér, Dan, Department of Oncology/Pathology, Karolinska Hospital, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Genetik, cytogenetik, cytogenetics, Genetics, HEN1, differentiation, LMO, LIM proteins, TAL1, T-ALL, bHLH
pages
111 pages
publisher
Anders hansson, Lund University, Department of Laboratory Medicine, Division of Molecular Medicine, Entrance 78, 3rd floor, U-MAS, 205 02 Malmö, Sweden,
defense location
Main lecture hall, Pathology Building (Entrance 78), U-MAS, Malmö
defense date
2004-02-27 10:15
ISBN
91-89625-30-7
language
English
LU publication?
yes
id
afc61e1e-c775-4edd-857e-428b8a98b0d7 (old id 466647)
date added to LUP
2007-09-07 13:38:32
date last changed
2016-09-19 08:45:14
@misc{afc61e1e-c775-4edd-857e-428b8a98b0d7,
  abstract     = {Acute lymphoblastic leukemia (ALL) is the most widespread type of cancer, as well as the most frequent leukemia in children. Malignant ALL cells originate from normal T lymphocytes or B cells that are blocked at immature stages of differentiation. Since T cell lineage derived ALL in children is associated with various unfavorable features, it is no surprise that childhood T lineage ALL have been reported to have a worse prognosis than childhood B lineage ALL. However, the development of new diagnostic and therapeutic strategies have, in recent years improved the outcome for children with T cell ALL. Yet, the molecular basis of pathogenesis remains largely unknown. A number of transcription factors involved in normal blood cell development, have been shown to induce T cell malignancies when aberrantly expressed in T cells. However, the mechanisms by which these proteins contribute to tumorigenesis are essentially undefined. This study has focused on the normal and oncogenic pathways of two such transcription factors, termed LMO2 and TAL1, both crucial for normal blood development as well as implicated in the genesis of a subset of T cell leukemias. We have also investigated the functions of LMO2 and TAL1 related proteins. Here we show that the pTa and p16 genes are potential target genes for TAL1, indicating that TAL1 might interfere with both differentiation and cell cycle control. Thus, suggesting that TAL1 might possess dual tumorigenic qualities. Moreover, we demonstrate that LMO2 is involved in erythropoiesis.},
  author       = {Hansson, Anders},
  isbn         = {91-89625-30-7},
  keyword      = {Genetik,cytogenetik,cytogenetics,Genetics,HEN1,differentiation,LMO,LIM proteins,TAL1,T-ALL,bHLH},
  language     = {eng},
  pages        = {111},
  publisher    = {ARRAY(0x83572c0)},
  title        = {Transcriptional regulation and effects on differentiation by LMO proteins and the basic helix-loop-helix factors TAL1 and HEN1},
  year         = {2004},
}