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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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; Servin, Anna; Anagnostaki, Lola; Linderoth, Johan; Berglund, Mattias; Soderberg, Ola; Enblad, Gunilla; Rosen, Anders; Mustelin, Tomas; Jerkeman, Mats; Persson, Jenny L; Gjörloff Wingren, Anette.

I: Leukemia & Lymphoma, Vol. 48, Nr. 11, 2007, s. 2221-2232.

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Fridberg, Marie ; Servin, Anna ; Anagnostaki, Lola ; Linderoth, Johan ; Berglund, Mattias ; Soderberg, Ola ; Enblad, Gunilla ; Rosen, Anders ; Mustelin, Tomas ; Jerkeman, Mats ; Persson, Jenny L ; Gjörloff Wingren, Anette. / 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. I: Leukemia & Lymphoma. 2007 ; Vol. 48, Nr. 11. s. 2221-2232.

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TY - JOUR

T1 - 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

AU - Fridberg, Marie

AU - Servin, Anna

AU - Anagnostaki, Lola

AU - Linderoth, Johan

AU - Berglund, Mattias

AU - Soderberg, Ola

AU - Enblad, Gunilla

AU - Rosen, Anders

AU - Mustelin, Tomas

AU - Jerkeman, Mats

AU - Persson, Jenny L

AU - Gjörloff Wingren, Anette

N1 - Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:32.

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - B cell

KW - lymphoma

KW - germinal center

KW - DLBCL

KW - ZAP70

KW - PKC-β

U2 - 10.1080/10428190701636443

DO - 10.1080/10428190701636443

M3 - Article

VL - 48

SP - 2221

EP - 2232

JO - Leukemia & Lymphoma

T2 - Leukemia & Lymphoma

JF - Leukemia & Lymphoma

SN - 1029-2403

IS - 11

ER -