Responses to Tumour initiating factors and Regulation of Normal and Malignant Haematopoiesis
Author
Summary, in English
Acute lymphoblastic leukaemia (ALL) is the most common malignancy among children. Contemporary treatment protocols result in cure rates of 80-85% but 15-20% of children still experience relapse. A group of patients do therefore not benefit from conventional therapy underlining the urgent need to identify additional biomarkers at diagnosis. We have investigated the expression of VEGF-A, its receptors VEGFR-1 and VEGFR-2 as well as PTEN and SHP1 in childhood ALL using immunohistochemistry. We observed that the expression of VEGFR-1, PTEN and SHP1 in mononuclear cells of children with ALL were significantly different to the expression of mononuclear cells in children with no malignant disease. VEGFR-1, PTEN and SHP1 may be potential prognostic factors for childhood ALL.
Chromosomal translocations are reported in approximately 65% of all acute leukaemias. Reports have identified leukaemic translocations in human peripheral blood of healthy individuals supporting the hypothesis that leukaemic transformation is a multistep process. The t(10;11)(p13-14;q14-21) translocation is a reciprocal translocation and forms both an in-frame CALM·AF10 and AF10·CALM fusion. The long latency period prior to the onset of leukaemia in CALM·AF10 mice models suggests that the fusion protein alone does not cause leukaemic development. We hypothesise that AF10·CALM is required for the full leukaemic phenotype. In an in vitro model, we found that t(10;11)(p13-14;q14-21) reciprocal fusions have individual effects on cell biology and, when found in combination, have either a more pronounced or an inhibitory effect on leukaemogenesis. This highlights the importance of examining both fusion proteins in a two transcript reciprocal translocation as they on their own may have individual characteristics.
Department/s
Publishing year
2010
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2010:76
Full text
Document type
Dissertation
Publisher
Center for Molecular Pathology, Faculty of Medicine
Topic
- Cell and Molecular Biology
- Cancer and Oncology
Status
Published
Research group
- Pathology, Malmö
Supervisor
- Göran Landberg
- Sven Påhlman
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-86443-92-4
Defence date
18 June 2010
Defence time
13:00
Defence place
Main lecture hall, Pathology building, entrance 78, Malmö University Hospital, Malmö
Opponent
- Dan Grandér (Prof. MD PhD)