CCR4 expression in a case of cutaneous Richter’s transformation of chronic lymphocytic leukaemia (CLL) to diffuse large B cell lymphoma (DLBCL) and in CLL patients with no skin manifestations

NANNINI P; BORGE M; MIKOLAITIS VC; ABREU C; MORANDE P; ZANETTI S; OPPEZZO P; BEZARES RF; GIORDANO M; GAMBERALE R

Congreso; First French-Argentine Immunology Congress; 2010

B cell chronic lymphocytic leukaemia (CLL) is characterized by a lymphocytosis of clonal CD5+ B lymphocytes. CLL transformation to Richter´s syndrome (RS) is a highly aggressive syndrome commonly represented by a diffuse large B-cell lymphoma (DLBCL) that arises from the original CLL clone. RS usually develops in lymph nodes and its cutaneous spread is very rare. CCR4 is the specific receptor for CCL17 and CCL22 (two chemokines highly produced in skin) and its expression was associated with normal and malignant T cell homing to skin and in a case of cutaneous DLBCL not related to CLL. Given that a skin RS transformation of CLL to DLBCL was detected in one of our patients, we hypothesized that his circulating CLL cells may express CCR4. We found that 11% of cutaneous CD19+ cells expressed CCR4, evaluated by flow cytometry, and more interestingly, also 7% of his circulating CLL cells were CCR4+ and were able to migrate towards CCL22 in a chemotaxis assay (CD19+ migration index to 0 and 2000 ng/ml of CCL22: 100 vs 145). In order to determine whether CCR4 expression was a special feature of this patient, we evaluated CCR4 expression on circulating CD19+ cells from CLL patients with no skin manifestations and elderly healthy donors. We found that CD19+ cells from these patients express similar levels of CCR4 but in a lower proportion than healthy donors (n=20, p<0.001). Moreover, CD19+CCR4+ cells might be more activated than the CCR4- ones, since the proportion of cells expressing the activation marker CD38 is higher in the former subpopulation (n=18, p<0.001). Since we reported that leukemic cells from CLL patients, independently of the presence of a cutaneous RS express CCR4, we can conclude that the expression of CCR4 on CLL cells seems not to be related to the cutaneous transformation of CLL cells. It remains to be determined whether the expression or functionality of CCR4 is augmented in leukemic cells of CLL patients who develop other skin manifestations.