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Visit our Expo - Redox and Inflammation signaling 2012

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Session II : Receptor <strong>signaling</strong> <strong>and</strong> G proteins Poster II, 8<br />

Expression of chemokine receptor CXCR4 (CD184) in B chronic lymphocytic leukaemia<br />

cells.<br />

Nicolaas H. C. Brons1, Valérie Palissot1, Chantal Schwartz1, Manon Bosseler1,<br />

Bernadette Leners1, Guy J Berchem1,2.<br />

1Laboratoire d'Hémato-Cancérologie Expérimentale, CRP-Santé, 84 Val Fleury, L1526<br />

Luxemb<strong>our</strong>g. E-mail : berchem.guy@chl.lu<br />

2Hémato-Cancérologie, Centre Hospitalier de Luxemb<strong>our</strong>g, 4 rue barblé, L1210<br />

Luxemb<strong>our</strong>g.<br />

Chronic lymphatic leukaemia (CLL) accounts for about 30% of adult leukemias in Western<br />

countries. This lymphoma is very indolent but relentless, with median survivals of almost a<br />

decade. The disease is characterized by the accumulation of a monoclonal population of CD5<br />

positive neoplastic B cells in secondary lymphoid organs, marrow, <strong>and</strong> blood. Although the<br />

slowly proliferating cells are sensitive to chemotherapeutic agents, chemotherapy is almost<br />

never curative <strong>and</strong> relapse inevitably follows. In 1975 Kanti Rai has described a clinical<br />

staging system which until now serves as basis for treatment decisions.<br />

The study was aimed to explore the CD184 also known as the CXCR4 chemokine receptor on<br />

B-lineage chronic lymphocyte leukaemia (B-CLL) cells of various disease stages <strong>and</strong> its<br />

relationship with others receptor expressions. CD 184 is expressed on CLL cells <strong>and</strong> normal<br />

B cells, it is one of the main receptors that mediate B cell entry in a secondary lymphoid<br />

tissues <strong>and</strong> their homing to T cell <strong>and</strong> B cell zones. Marrow stromal cells or nurselike cells<br />

constituvely secrete CXCR12, the lig<strong>and</strong> for CXCR4, thereby attracting <strong>and</strong> rescuing CLL B<br />

cells from apoptosis in a contact dependent fashion. Therefore, CD184 has been mentioned as<br />

a possible prognostic marker in CLL. Flow cytometry was used to detect the CXCR4<br />

expression in patients of different Rai stages The samples were measured on a FACSCanto<br />

(BD) <strong>and</strong> up to 6 markers per tube were analysed by the DivaSoftware (BD). Calibration<br />

curves for the MFE were obtained with Fluorospheres (DakoCytomation, K0110). More than<br />

thirty CD markers have been used to characterized B leukemic cells <strong>and</strong> correlation was<br />

researched with CD184. Of the 44 persons , 11 were healthy donors, 5 had Rai stage 0<br />

disease, 12 had Rai stage I disease, 3 had Rai stage II disease, 4 had Rai stage III disease, 9<br />

had Rai stage IV disease. CXCR4 was consistently expressed on circulating B-CLL with a<br />

mean fluorescence intensity higher than in cells from healthy volunteers. There was a<br />

correlation between CXCR4 expression <strong>and</strong> late stage of the disease. Interestingly,<br />

chemotherapeutic treatments seem to decrease level of this marker down to level of earliest<br />

stages. However, there was no correlation of CD184 level <strong>and</strong> quantitative expressions of<br />

known CD markers tested. Different correlations with previous treatments <strong>and</strong> known<br />

prognostic factors will be described <strong>and</strong> clinical implications will be discussed.<br />

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