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 upregulation 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.