The role of 9-O-acetylated ganglioside D3 (CD60) and {alpha}4{beta}1 (CD49d) expression in predicting the survival of patients with Sezary syndrome.
BACKGROUND
Sézary 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.


METHODS
We 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.


RESULTS
We 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(+)CD60(+) cells (≥ 0.5×10(9)/L) and low proportion of CD4(+)CD49d(+) cells (<0.5×10(9)/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.


CONCLUSIONS
In 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.
Scala
Enrico
E
Center for Molecular Allergology, IDI-IRCCS, Via dei Monti di Creta 104, I-00167 Rome, Italy. e.scala@idi.it
Abeni
Damiano
D
Pomponi
Debora
D
Narducci
Maria Grazia
MG
Lombardo
Giuseppe Alfonso
GA
Mari
Adriano
A
Frontani
Marina
M
Picchio
Maria Cristina
MC
Pilla
Maria Antonietta
MA
Caprini
Elisabetta
E
Russo
Giandomenico
G
D000328:Adult; D000368:Aged; D019011:Antigens, CD7 / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005732:Gangliosides / Q000097:blood*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039441:Integrin alpha4 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012751:Sezary Syndrome / Q000097:blood / Q000401:mortality; D012878:Skin Neoplasms / Q000097:blood / Q000401:mortality; D015996:Survival Rate
D019011:Antigens, CD7; D014408:Biomarkers, Tumor; D005732:Gangliosides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D039441:Integrin alpha4; C049132:9-O-acetyl-GD3 ganglioside; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4