Expression of CCR4 in adult T-cell leukemia

Abstract

Adult T-cell leukemia (ATL) is a malignancy of mature T cells that is etiologically associated with human T-cell leukemia virus type 1 (HTLV-1). The frequent manifestation of ATL is infiltration of leukemic cells into various organs. Besides certain cell adhesion molecules and matrix metalloproteineses, chemokine receptors may play important roles in tissue infiltration of ATL. Identification of a unique set of chemokine receptors expressed by ATL would thus provide valuable information about the molecular mechanism of tissue infiltration of ATL. This may also reveal that ATL frequently develops from a certain subset of T cells that express a particular set of chemokine receptors. Since HTLV-1 encodes a potent viral transcriptional activator Tax, which is known to induce various cellular genes, expression of some chemokine receptors may be affected by Tax. This, however, may relate more to HTLV-1-infected T cells, since ATL cells usually do not express Tax. Finally, identification of a unique set of chemokine receptors expressed by ATL may also provide a new therapeutic target. These considerations prompted us to examine the chemokine receptor expression in ATL. We found that in the majority of ATL cases, leukemic cells consistently express CCR4. Since CCR4 is known to be involved in T cell migration into skin, this may in part explain the frequent skin infiltration in ATL. Furthermore, CCR4 is known to be selectively expressed by Th2 and regulatory T cells. Thus, the majority of ATL may predominantly originate from either Th2 or regulatory T cells.