The detailed evaluation of HRQoL and psychological problems in patients with cutaneous lymphomas, and their relationship with clinical variables, may give important information on the burden of the disease for patients, and thus improve communication and satisfaction with care.

Sé zary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin Tcell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/ dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26 ؊ phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26 ؉ CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26. IntroductionCutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas (NHLs) that show a considerable variability in clinical presentation, histology, immunophenotype, and prognosis. They represent a clonal malignancy 1 of CD4 ϩ helper T cells 2,3 with a memory phenotype 4 and tendency to accumulate in the skin. 5 Mycosis fungoides (MF) and Sézary syndrome (SS) are the 2 major clinical variants of CTCLs. While MF shows a skinrestricted infiltration of the clonal T-cell population and an indolent course, SS is a leukemic and erythrodermic variant of CTCL characterized by the presence of tumor lymphocytes in the skin, lymph nodes, and peripheral blood. These tumor cells, named SS cells, have major abnormalities like a low mitotic index, aberrant but nonuniform chromosomal alterations, 6 monoclonal rearrangement 7 with a loss of T-cell receptor repertoire complexity 8 and loss of surface molecules such as CD7, CD26, and CD49d. 9-11 SS cells mainly localize to the skin and express cutaneous lymphocyteassociated antigen (CLA) that has been implicated in skin-specific homing patterns. 4,9 However, the mechanisms underlying the accumulation of these atypical lymphocytes to the skin are poorly defined. Extravasation and active locomotion of malignant lymphocytes could suggest the involvement of secreted factors such as chemokines. Chemokines regulate multiple cell functions, including cell chemotaxis, proliferation, and apoptosis, and are involved in leukocyte transendothelial migration and homing to tissues.These biologic activities are mediated through their interaction with G protein-coupled chemokine receptors expressed by target cells such as leukocytes, hematopoietic cells, neuronal cells, glial cells, and cells of the vasculat...

Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma and its pathogenesis is still unknown. Diagnosis/prognosis may strongly ameliorate the management of SS individuals. Here, we profiled the expression of 470 microRNAs (miRNAs) in a cohort of 22 SS patients, and we identified 45 miRNAs differentially expressed between SS and controls. Using predictive analysis, a list of 19 miRNAs, including miR-21, miR-214, miR-486, miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs including again miR-21, potentially able to discriminate patients with unfavorable and favorable outcome. We validated our data for miR-21, miR-214 and miR-486 by qRT-PCR, including an additional set of array-independent SS cases. In addition, we also provide an in vitro evidence for a contribution of miR-214, miR-486 and miR-21 to apoptotic resistance of CTCL cell line.