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Rezeptor-Tyrosinkinasen in Hodgkin-Lymphomen als mögliche Angriffspunkte neuer Therapieoptionen

Receptor tyrosine kinases in Hodgkin lymphoma as possible therapeutic targets

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Zusammenfassung

Hodgkin-Lymphome (HL) sind die häufigsten nodalen Lymphome in Europa. Die von B-Zellen abstammenden Hodgkin-Reed-Sternberg- (HRS-) Zellen zeigen einen nahezu vollständigen Verlust ihres B-Zell-Phänotyps. In etwa 40% aller HL ist das Epstein-Barr-Virus (EBV) nachweisbar. Für Vorläufer der HRS-Zellen stellt EBV wahrscheinlich einen Schutz vor Apoptose dar. Histologisch finden sich nur einzelne HRS-Zellen in einem gemischtzellulären entzündlichen Infiltrat. Das Zusammenspiel zwischen den HRS-Zellen und diesem zellulären Infiltrat ist für HL von zentraler Bedeutung, die sich in einer Vielzahl von parakrinen Aktivierungsmechanismen widerspiegelt. Daneben sind auch zahlreiche autokrine Stimulationsmechanismen in HRS-Zellen bekannt. Die aberrante Expression und Aktivierung 7 verschiedener Rezeptor-Tyrosinkinasen in HL stellt dabei einen Aktivierungsmechanismus von besonderem Interesse dar, da eine Reihe verschiedener Antikörper und niedermolekularer Substanzen zur Inhibition von Rezeptor-Tyrosinkinasen bereits klinisch zur Therapie verschiedenster Tumorentitäten eingesetzt wird. Die Blockade von Rezeptor-Tyrosinkinasen könnte daher auch in HL eine neue Therapieoption darstellen.

Abstract

Hodgkin lymphoma (HL) is the most frequent nodal lymphoma in Europe. The B-cell derived Hodgkin-Reed Sternberg (HRS) cells are nearly completely deficient for expression of B-cell markers. Epstein-Barr virus (EBV) can be detected in about 40% of HL cases. Presumably, EBV protects HRS cell precursors from apoptosis. Histologically only single HRS cells are dispersed in a broad reactive cellular background. Interactions between HRS cells and their surrounding cellular infiltrate, among them paracrine activation of several signalling pathways, is crucial in HL. HRS cells also show autocrine activation of several signalling pathways. Among these, the aberrant expression and activation of seven different receptor tyrosine kinases (RTK) is of special interest, as many different antibodies and low molecular substances which inhibit RTK activity are already in clinical use for anticancer therapy. Therefore, blocking of RTK activities in HL may be a novel therapeutic option.

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Abbreviations

CCL28:

Chemokinrezeptorligand 28

cHL:

Klassisches Hodgkin-Lymphom

EBF:

„Early B cell factor“

EBV:

Epstein-Barr-Virus

EGFR:

„Epidermal growth factor receptor“

EPHB1:

„Ephrin type B receptor 1“

FLT3:

„FMS-related tyrosine kinase 3“

HER2:

„Human epidermal growth receptor 2“

HL:

Hodgkin-Lymphom

HRS-Zellen:

Hodgkin-Reed-Sternberg-Zellen

ID:

„Inhibitor of DNA-binding“

IL:

Interleukin

JAK:

Januskinase

LMP-1:

„Late membrane protein 1“

lpHL:

Lymphozyten-prädominantes Hodgkin-Lymphom

NF-κB:

Nukleärer Faktor kappa B

NGFβ:

„Nerve growth factor beta“

PDGFRA:

„Platelet-derived growth factor receptor“

PI3K:

Phosphatidylinositol-3-Kinase

RTK:

Rezeptor-Tyrosinkinasen

SOCS:

„Suppressor of cytokine signaling“

STAT:

„Signal transducers and activators of transcription“

TARC:

„Thymus and activation regulated chemokine“

TIE1:

„Tyrosin kinase with Ig and EGF homology domain“

TK:

Tyrosinkinase

TNF-α:

Tumor-Nekrose-Faktor alpha

TRKA:

„Tropomyosine related kinase A“

TRKB:

„Tropomyosine related kinase B“

WHO:

World Health Organisation

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Authors and Affiliations

  1. Senckenbergisches Institut für Pathologie, Universitätsklinikum, Theodor-Stern-Kai 7, 60596 , Frankfurt am Main, Deutschland

    C. Renné & M.L. Hansmann

  2. Gerhard- Domagk-Institut für Pathologie, Universitätsklinikum Münster, Münster, Deutschland

    A. Bräuninger

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  1. C. Renné
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  2. M.L. Hansmann
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  3. A. Bräuninger
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Correspondence to C. Renné.

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Renné, C., Hansmann, M. & Bräuninger, A. Rezeptor-Tyrosinkinasen in Hodgkin-Lymphomen als mögliche Angriffspunkte neuer Therapieoptionen. Pathologe 30, 393–400 (2009). https://doi.org/10.1007/s00292-009-1157-9

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  • DOI: https://doi.org/10.1007/s00292-009-1157-9

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