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Protein kinases and phosphatases in B-cell lymphoma

Fridberg, Marie LU (2009) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2009:101.
Abstract
Around 2000 persons are diagnosed with lymphoma in Sweden each year. There are many subgroups described for this form of cancer and the great majority is derived from B-cells. The most common subgroup is Diffuse large B-cell lymphoma (DLBCL), a highly aggressive disease where only half of the patients are cured. The lymphoma types seen in adults and children vary and the dominant form in children is the B-cell derived Burkitt lymphoma (BL). In contrast to DLBCL, high survival rates in BL are obtained but more research on normal- and tumor B-cells is needed for a better understanding of the cellular mechanisms underlying lymphoma pathogenesis. Phosphorylation and dephosphorylation of enzymes are key events in signal transduction in cells.... (More)
Around 2000 persons are diagnosed with lymphoma in Sweden each year. There are many subgroups described for this form of cancer and the great majority is derived from B-cells. The most common subgroup is Diffuse large B-cell lymphoma (DLBCL), a highly aggressive disease where only half of the patients are cured. The lymphoma types seen in adults and children vary and the dominant form in children is the B-cell derived Burkitt lymphoma (BL). In contrast to DLBCL, high survival rates in BL are obtained but more research on normal- and tumor B-cells is needed for a better understanding of the cellular mechanisms underlying lymphoma pathogenesis. Phosphorylation and dephosphorylation of enzymes are key events in signal transduction in cells. Protein kinases phosphorylate enzymes while protein phosphatases dephosphorylate them, and these opposite actions must be carefully balanced for normal cell division to occur. The aim of this study was to characterize B-cell lymphomas with emphasis on a panel of kinases and phosphatases previously described as oncogenes (kinases) and tumorsuppressors (phosphatases) in human cancers. We analyzed DLBCL tissue and found the kinases PKC-β II and ZAP70 to be stronger expressed at protein level in a subgroup of the disease associated with poor survival. We further report enhanced activation of DLBCL cells through the B-cell receptor when ZAP70 is introduced. Also, the protein expression of the phosphatases HePTP and PTEN are weaker in BL tissue from children compared to in non-malignant pediatric controls. Our results indicate important roles for the described kinases and phosphatases in B-cell lymphomas. (Less)
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author
supervisor
opponent
  • Professor Jönsson, Jan-Ingvar, Linköping University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
HePTP, PTEN, PKC-beta 2, B-cell, lymphoma, kinases, ZAP70, phosphatase, SHP2
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2009:101
pages
102 pages
publisher
Inst för Laboratoriemedicin, Avd för tumörbiologi, Malmö Universitetssjukhus, Lunds Universitet
defense location
Patologen, ingång 78
defense date
2009-10-30 09:00
ISSN
1652-8220
ISBN
978-91-86253-89-9
language
English
LU publication?
yes
id
f7c4b01a-9989-4519-98d6-b88241f13778 (old id 1487397)
date added to LUP
2009-10-12 11:58:57
date last changed
2016-09-19 08:44:50
@phdthesis{f7c4b01a-9989-4519-98d6-b88241f13778,
  abstract     = {Around 2000 persons are diagnosed with lymphoma in Sweden each year. There are many subgroups described for this form of cancer and the great majority is derived from B-cells. The most common subgroup is Diffuse large B-cell lymphoma (DLBCL), a highly aggressive disease where only half of the patients are cured. The lymphoma types seen in adults and children vary and the dominant form in children is the B-cell derived Burkitt lymphoma (BL). In contrast to DLBCL, high survival rates in BL are obtained but more research on normal- and tumor B-cells is needed for a better understanding of the cellular mechanisms underlying lymphoma pathogenesis. Phosphorylation and dephosphorylation of enzymes are key events in signal transduction in cells. Protein kinases phosphorylate enzymes while protein phosphatases dephosphorylate them, and these opposite actions must be carefully balanced for normal cell division to occur. The aim of this study was to characterize B-cell lymphomas with emphasis on a panel of kinases and phosphatases previously described as oncogenes (kinases) and tumorsuppressors (phosphatases) in human cancers. We analyzed DLBCL tissue and found the kinases PKC-β II and ZAP70 to be stronger expressed at protein level in a subgroup of the disease associated with poor survival. We further report enhanced activation of DLBCL cells through the B-cell receptor when ZAP70 is introduced. Also, the protein expression of the phosphatases HePTP and PTEN are weaker in BL tissue from children compared to in non-malignant pediatric controls. Our results indicate important roles for the described kinases and phosphatases in B-cell lymphomas.},
  author       = {Fridberg, Marie},
  isbn         = {978-91-86253-89-9},
  issn         = {1652-8220},
  keyword      = {HePTP,PTEN,PKC-beta 2,B-cell,lymphoma,kinases,ZAP70,phosphatase,SHP2},
  language     = {eng},
  pages        = {102},
  publisher    = {Inst för Laboratoriemedicin, Avd för tumörbiologi, Malmö Universitetssjukhus, Lunds Universitet},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Protein kinases and phosphatases in B-cell lymphoma},
  volume       = {2009:101},
  year         = {2009},
}