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Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: Higher expression of ZAP70 and PKC-beta II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN

Fridberg, Marie LU ; Servin, Anna ; Anagnostaki, Lola ; Linderoth, Johan LU ; Berglund, Mattias ; Soderberg, Ola ; Enblad, Gunilla ; Rosen, Anders ; Mustelin, Tomas and Jerkeman, Mats LU , et al. (2007) In Leukemia & Lymphoma 48(11). p.2221-2232
Abstract
Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-beta I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-beta II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically... (More)
Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-beta I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-beta II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically favourable GC group. Also, the subcellular localization of PKC-beta I and II differed in DLBCL cells, with the PKC-beta I isoform being expressed in both the cytoplasm and nucleus, while PKC-beta II was found exclusively in the cytoplasm. Loss of nuclear PTEN correlated with poor survival in cases from both subgroups. In addition, five cell lines of DLBCL origin were analyzed for protein expression and for mRNA levels of PTEN and SHP1. For the first time, we show that ZAP70 is expressed in a higher percentage of tumor cells in the aggressive non-GC subgroup of DLBCL and that PKC-beta I and II are differently distributed in the two prognostic subgroups of de novo DLBCL. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
B cell, lymphoma, germinal center, DLBCL, ZAP70, PKC-β
in
Leukemia & Lymphoma
volume
48
issue
11
pages
2221 - 2232
publisher
Taylor & Francis
external identifiers
  • pmid:17926183
  • wos:000250839100022
  • scopus:36048935750
ISSN
1042-8194
DOI
10.1080/10428190701636443
language
English
LU publication?
yes
additional info
Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:32.
id
ccfa6bfa-a9f5-4ee8-a633-dd7735c27a4e (old id 1138039)
date added to LUP
2016-04-01 16:24:01
date last changed
2022-03-15 00:13:01
@article{ccfa6bfa-a9f5-4ee8-a633-dd7735c27a4e,
  abstract     = {{Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-beta I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-beta II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically favourable GC group. Also, the subcellular localization of PKC-beta I and II differed in DLBCL cells, with the PKC-beta I isoform being expressed in both the cytoplasm and nucleus, while PKC-beta II was found exclusively in the cytoplasm. Loss of nuclear PTEN correlated with poor survival in cases from both subgroups. In addition, five cell lines of DLBCL origin were analyzed for protein expression and for mRNA levels of PTEN and SHP1. For the first time, we show that ZAP70 is expressed in a higher percentage of tumor cells in the aggressive non-GC subgroup of DLBCL and that PKC-beta I and II are differently distributed in the two prognostic subgroups of de novo DLBCL.}},
  author       = {{Fridberg, Marie and Servin, Anna and Anagnostaki, Lola and Linderoth, Johan and Berglund, Mattias and Soderberg, Ola and Enblad, Gunilla and Rosen, Anders and Mustelin, Tomas and Jerkeman, Mats and Persson, Jenny L and Gjörloff Wingren, Anette}},
  issn         = {{1042-8194}},
  keywords     = {{B cell; lymphoma; germinal center; DLBCL; ZAP70; PKC-β}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2221--2232}},
  publisher    = {{Taylor & Francis}},
  series       = {{Leukemia & Lymphoma}},
  title        = {{Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: Higher expression of ZAP70 and PKC-beta II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN}},
  url          = {{http://dx.doi.org/10.1080/10428190701636443}},
  doi          = {{10.1080/10428190701636443}},
  volume       = {{48}},
  year         = {{2007}},
}