Autocrine NGFbeta/TRKA signalling is an important survival factor for Hodgkin lymphoma derived cell lines.
Hodgkin-Reed/Sternberg cells, the tumor cells of Hodgkin lymphoma, aberrantly express several receptor tyrosine kinases, among them TRKA whose stimulation supports B cell survival. We show here high expression of TRKA in Hodgkin-Reed/Sternberg cell lines as compared to normal B cells and other B cell lymphomas, without major increases in TRKA gene dosage. A fraction of TRKA is constitutively activated, likely due to the coexpression of NGFbeta, the TRKA high affinity ligand. The TRK inhibitor K-252a decreased survival of Hodgkin-Reed/Sternberg cell lines accompanied by decreased AKT activation. Inclusion of TRK inhibitors in therapeutic regimens may thus be an interesting possibility.
Senckenberg Institute of Pathology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Christoph
C
Renné
Sarah
S
Minner
Ralf
R
Küppers
Martin-Leo
ML
Hansmann
Andreas
A
Bräuninger
D001402:B-Lymphocytes; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D006689:Hodgkin Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D026121:Indole Alkaloids / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
D002227:Carbazoles; D026121:Indole Alkaloids; C502240:NGF protein, human; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020917:Receptor, trkA