Increase in clusterin forms part of the stress response in Hodgkin's lymphoma.
Clusterin (also called APOJ, SGP-2, XIP8) has thus far been only partially characterized in lymphomas contrary to other types of cancer. Its expression has been reported only for anaplastic large cell lymphomas and, more recently, in mycosis fungoides. Here, we demonstrate an up-regulation of intracellular clusterin in Hodgkin's lymphoma (HL)-derived cell lines L-428, KM-H2 and L-540, caused by different stimuli such as IFN-γ, doxorubicin and X-rays. These stimuli are relevant for the pathophysiology and therapy of HL and represent a first step in the characterisation of this glycoprotein known to have a role in drug chemoresistance. p53 up-regulation accompanies increases in clusterin levels accordingly with the onset of apoptosis. We also show that the cells secrete more clusterin after treatment with doxorubicin, which is consistent with the observed intracellular increase. These observations suggested that the levels of circulating clusterin should also be measured in the peripheral blood from HL patients both at the time of diagnosis and after two cycles of chemotherapy. In a preliminary study on patient sera we observed that an increase in clusterin is correlated with positron emission tomography (PET) positivity after two cycles of chemotherapy.
Hematology Division, Azienda Ospedaliera S. Maria Nuova, Reggio Emilia, Italy.
Raffaele
R
Frazzi
Bruno
B
Casali
Mauro
M
Iori
Davide
D
Nicoli
Caterina
C
Mammi
Francesco
F
Merli
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051152:Clusterin / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D006689:Hodgkin Disease / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D011379:Prognosis; D011829:Radiation Dosage; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051152:Clusterin; D004317:Doxorubicin; D007371:Interferon-gamma