The role of 9-O-acetylated ganglioside D3 (CD60) and  4 1 (CD49d) expression in predicting the survival of patients with Sezary syndrome

Abstract

BackgroundSézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4 + T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20¥10 9 /L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described. Design and MethodsWe used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4 + T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan-Meier product-limit estimates and hazard ratios from the Cox proportional hazards model. ResultsWe found that both higher number of CD60 + and lower number of CD49d + cells within circulating CD4 + T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4 /L) (hazard ratio = 12.303, 95% confidence interval 1.5-95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1. ConclusionsIn this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4 + T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome.Key words: TCR-Vβ repertoire, CD60, CD49d, survival rate, Sézary syndrome. Haematologica 2010;95(11):1905-1912. doi:10.3324/haematol.2010 This is an open-access paper.The role of 9-O-acetylated ganglioside D3 (CD60) and α4β1 (CD49d) expression in predicting the survival of patients with Sézary syndrome

Erythrodermic cutaneous T-cell lymphoma: How to differentiate this rare disease from atopic dermatitis

“…As circulating T cells in patients with benign inflammatory skin diseases may also show CD7 deletion [31,33], loss of CD26 may be a more specific phenotype for Sé zary cells [32]. Besides, Sé zary cells over-express CD60 and lack CD49d [34,35]. Recently, CD158k/KIR3DL2, which is an MHC class I antigen receptor that belongs to the family of natural killer (NK) cell immunoglobulin-like receptors, has been identified as a new phenotypic marker for circulating Sé zary cells [36].…”

CD164 identifies CD4+ T cells highly expressing genes associated with malignancy in Sézary syndrome: the Sézary signature genes, FCRL3, Tox, and miR-214

“…The presence of such biomarker (s) will aid in diagnosis and monitoring of the disease as well as in designing effective treatments targeting malignant cells and sparing of normal immunocompetent cells. Several surface molecules, namely NKp46, syndycan 4 (SD-4), ganglioside GD3 (CD60), mucin 1 (Muc 1) and CD158k/KIR3DL2 have been found to be highly expressed on CD4 + T cells from some SS patients compared with healthy controls [5, 9, 19, 36, 37]. SD-4, CD60 and Muc-1 molecules are also upregulated on activated normal CD4 + T cells [1, 8, 27].…”

Single-cell heterogeneity in Sézary syndrome

“…These include high scatter characteristics with abnormal Sézary cell morphology, as well as increased expression of CD60, CD158k (KIR3DL2), CD164, and CD307c (FCRL3) and loss of expression of CD2, CD7, CD26, and CD49d. 15,[26][27][28][29][30][31] In our SS cohort, we obtained the most consistently defined malignant population using CD7 and CD26 together with the dominant TCRVb clone (when possible). Although the vast majority of nonmalignant T cells are CD26 1 CD7 1 , a minority of these cells may lose expression of CD7 and CD26.…”

“…Although the vast majority of nonmalignant T cells are CD26 1 CD7 1 , a minority of these cells may lose expression of CD7 and CD26. 27 As a consequence, in the absence of more selective markers of malignancy, gating malignant cells as non-CD26 1 CD7 1 cells potentially allows a minor fraction of nonmalignant T cells to be included in the malignant population. We have not directly assessed this possible contamination, but the magnitude can be estimated by the presence of polyclonal T cells within the non-CD26 1 CD7 1 population for patients with a malignant population unmarked by the TCRVb screening kit (2.5%-12.9%; Figure 1B).…”