The correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukaemia (CLL) [i.e., mutational status of the immunoglobulin heavy chain variable region (IgV(H)), ZAP-70- and CD38-expression] and adiponectin serum concentration was evaluated in a cohort of 69 previously untreated Binet stage A CLL patients. Adiponectin levels inversely correlated with absolute peripheral blood lymphocyte count (r = -0.254; P = 0.03), CD38-positive CLL cells (r = -0.294; P = 0.04) and ZAP-70 (r = -0.285; P = 0.03). The univariate Cox proportional hazard model demonstrated that, in addition with lower serum levels of adiponectin (P = 0.01), the unmutated IgV(H) condition (P = 0.002) and ZAP-70-positivity (P = 0.02) were associated with a shorter time to first treatment (TFT). However, in multivariate analysis only ZAP-70 positivity emerged as predictor of the TFT (P = 0.008). The levels of adiponectin in CLL were evaluated in 60 patients from an independent cohort investigated by gene expression profiling. Adiponectin gene expression was invariably low suggesting a limited (if any) role of leukemic cells in the production of circulating adiponectin levels. In contrast, both adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA were highly expressed by CLL cells with a degree of inter-patient variability. Our results, although preliminary, lend support to the idea that adiponectin secretion by bone marrow adipocytes might represent a possible promising drug target in the field of hematology.
Prognostic relevance of serum levels and cellular expression of adiponectin in B-cell chronic lymphocytic leukemia / S. Molica, G. Vitelli, G. Cutrona, K. Todoerti, R. Mirabelli, G. Digiesi, D. Giannarelli, I. Sperduti, M. Molica, M. Gentile, F. Morabito, A. Neri, M. Ferrarini. - In: INTERNATIONAL JOURNAL OF HEMATOLOGY. - ISSN 0925-5710. - 88:4(2008 Nov), pp. 374-380.
Prognostic relevance of serum levels and cellular expression of adiponectin in B-cell chronic lymphocytic leukemia
K. Todoerti;A. NeriPenultimo
;
2008
Abstract
The correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukaemia (CLL) [i.e., mutational status of the immunoglobulin heavy chain variable region (IgV(H)), ZAP-70- and CD38-expression] and adiponectin serum concentration was evaluated in a cohort of 69 previously untreated Binet stage A CLL patients. Adiponectin levels inversely correlated with absolute peripheral blood lymphocyte count (r = -0.254; P = 0.03), CD38-positive CLL cells (r = -0.294; P = 0.04) and ZAP-70 (r = -0.285; P = 0.03). The univariate Cox proportional hazard model demonstrated that, in addition with lower serum levels of adiponectin (P = 0.01), the unmutated IgV(H) condition (P = 0.002) and ZAP-70-positivity (P = 0.02) were associated with a shorter time to first treatment (TFT). However, in multivariate analysis only ZAP-70 positivity emerged as predictor of the TFT (P = 0.008). The levels of adiponectin in CLL were evaluated in 60 patients from an independent cohort investigated by gene expression profiling. Adiponectin gene expression was invariably low suggesting a limited (if any) role of leukemic cells in the production of circulating adiponectin levels. In contrast, both adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA were highly expressed by CLL cells with a degree of inter-patient variability. Our results, although preliminary, lend support to the idea that adiponectin secretion by bone marrow adipocytes might represent a possible promising drug target in the field of hematology.Pubblicazioni consigliate
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