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

Abstract

Objective: Richter's transformation of B-cell chronic lymphocytic leukemia (CLL) to cutaneous diffuse large B-cell lymphoma (DLBCL) is very rare. We took the advantage of one of these cases to test the hypothesis that the chemokine receptor CCR4 is involved in the homing of CLL cells to skin.

Patients and methods: We evaluated CCR4 expression by flow cytometry in both circulating and skin CD19(+) leukemic cells from a patient with cutaneous DLBCL. As controls, we used peripheral blood samples from CLL patients without skin manifestations and from elderly healthy donors.

Results: We found that both DLBCL cells derived from the original CLL clone and circulating CLL cells from this patient expressed CCR4. Although it was previously reported that CCR4 is not expressed in CLL cells, we found that a low but significant proportion of leukemic cells from CLL patients with no skin manifestations do express CCR4. There was a positive correlation between the expression of CCR4 and the percentage of ZAP-70 of each sample. Moreover, we consistently observed a higher expression of CCR4 within CD19(+)CD38(+) and CD19(+)Ki67(+) subsets compared to CD19(+)CD38(-) and CD19(+)Ki67(-) lymphocytes from the same sample, respectively.

Conclusion: We conclude that the chemokine receptor CCR4 is not a special feature of CLL cells with skin manifestation, but rather it is expressed in a low but significant proportion of peripheral blood CLL cells.