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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)

MEDICAL AND HEALTH SCIENCES  (hsv//eng)

Nyckelord

MEDICINE Morphology, cell biology, pathology Cell biology Medical cell biology

MEDICIN Morfologi, cellbiologi, patologi Cellbiologi Medicinsk cellbiologi

MEDICINE Microbiology, immunology, infectious diseases Immunology Tumour immunology

MEDICIN Mikrobiologi, immunologi, infektionssjukdomar Immunologi Tumörimmunologi

MEDICINE

MEDICIN

Medicine

B cell

DLBCL

Germinal center

Lymphoma

PKC-β

ZAP70

lymphoma

germinal center

PKC-ß

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