P065 Acute crisis of adult T-cell leukaemia following soluble CD30 elevation: Shedding of CD30 and CD25 from cell surface associated with the aggressiveness

Abstract

Introduction Adult T-cell leukaemia/lymphoma (ATL) caused by human retrovirus, HTLV-1, is a neoplasm of mature T-cell. In Japan, more than a thousand patients with ATL die every year because this disease still remains incurable. Acute crisis is a common phenomenon of chronic leukaemia and indolent haematological malignancy, in which proliferation of leukaemic cells is accelerated following a certain term of chronic phase. Although some genetic changes are thought to be responsible for this sudden change of characteristics in leukaemic cells, it has been unclear if they are the cause or the result of crisis. Methods We assessed the therapy and outcome of 79 newly diagnosed or referred ATL patients from 2005 to 2010. Serum sample of patient was preserved in freezer to measure the level of soluble proteins, sCD30 and sIL-2R, using ELISA. The sIL-2R concentration in serum was measureed by Cell freeN IL-2R (Kyowa Medex, Japan) and Determiner CL IL-2R (Kyowa Medex, Japan). The sCD30 concentration in serum was measured by Human sCD30 Platinum ELISA (eBioscience). In the present study, patients with ATL chronic type were investigated by monitoring changes in the serum levels of sIL-2R and sCD30. Results Six patients showed acute crisis from chronic phase (the observed periods of chronic phase are 31–866 days) and increasing sCD30 level as well as sIL-2R elevation was found as an earlier event of the acute crisis (average levels of sCD30 and sIL-2R were 2029 U/ml and 14035 U/ml in acute crisis; 341 U/ml and 5008 U/ml in chronic phase). In contrast, average of sCD30 and sIL-2R in 25 HTLV-1 carriers are 37 U/ml and 428 U/ml, respectively. Although the patterns and levels of soluble proteins elevation were unique to each case, serum sCD30 level predominantly elevated at the crisis. Interestingly, CD30 is not always detected on the surface of ATL cells. Chronic inflammation caused by constituvive activation of STATs may be associated with Matrix Metalloproteinase activation which sheds CD30 from the surface of ATL cells. Conclusion Our findings suggest that soluble protein levels in sera of patients are useful biological markers for diagnosis and therapy of ATL. Furthermore, since spontaneous remission was observed during the insufficinet level of serum sCD30 by comparison to the sIL-2R level, it is conceivable that the sCD30 protects CD30+ leukaemic stem cells from CD30 ligand-mediated cell death.