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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • B cell, lymphoma, germinal center, DLBCL, ZAP70, PKC-β
Original languageEnglish
Pages (from-to)2221-2232
JournalLeukemia & Lymphoma
Volume48
Issue number11
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:32.

Related research output

Fridberg, M., 2009, Inst för Laboratoriemedicin, Avd för tumörbiologi, Malmö Universitetssjukhus, Lunds Universitet. 102 p.

Research output: ThesisDoctoral Thesis (compilation)

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