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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

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Author

  • Marie Fridberg
  • Anna Servin
  • Lola Anagnostaki
  • Johan Linderoth
  • Mattias Berglund
  • Ola Soderberg
  • Gunilla Enblad
  • Anders Rosen
  • Tomas Mustelin
  • Mats Jerkeman
  • Jenny L Persson
  • Anette Gjörloff Wingren
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Summary, in English

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.

Publishing year

2007

Language

English

Pages

2221-2232

Publication/Series

Leukemia & Lymphoma

Volume

48

Issue

11

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Cancer and Oncology

Keywords

  • B cell
  • lymphoma
  • germinal center
  • DLBCL
  • ZAP70
  • PKC-β

Status

Published

Research group

  • Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1042-8194