Prognostic relevance of serum levels and cellular expression of adiponectin in B-cell chronic lymphocytic leukemia.
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.
Molica
Stefano
S
Medical Oncology Unit, Hematology-Oncology Department, Azienda Ospedaliera Pugliese-Ciaccio, Viale Pio X, 88100, Catanzaro, Italy. smolica@libero.it.
Vitelli
Gaetano
G
Clinical Pathology, IRCCS Regina Elena, Rome, Italy.
Cutrona
Giovanna
G
Medical Oncology C, IST, Genoa, Italy.
Todoerti
Katia
K
Leukemia Study Center, Department of Medical Sciences, University Milano, Hematology 1, Fondazione IRCCS Policlinico, Milan, Italy.
Mirabelli
Rosanna
R
Medical Oncology Unit, Hematology-Oncology Department, Azienda Ospedaliera Pugliese-Ciaccio, Viale Pio X, 88100, Catanzaro, Italy.
Digiesi
Giovanna
G
Clinical Pathology, IRCCS Regina Elena, Rome, Italy.
Giannarelli
Diana
D
Clinical Pathology, IRCCS Regina Elena, Rome, Italy.
Sperduti
Isabella
I
Clinical Pathology, IRCCS Regina Elena, Rome, Italy.
Molica
Matteo
M
Medical School La Sapienza, Rome, Italy.
Gentile
Massimo
M
Hematology Department, Az. Ospedaliera, Cosenza, Italy.
Morabito
Fortunato
F
Hematology Department, Az. Ospedaliera, Cosenza, Italy.
Neri
Antonino
A
Leukemia Study Center, Department of Medical Sciences, University Milano, Hematology 1, Fondazione IRCCS Policlinico, Milan, Italy.
Ferrarini
Manlio
M
Medical Oncology C, IST, Genoa, Italy.
D051997:ADP-ribosyl Cyclase 1; D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000097:blood / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D054419:Receptors, Adiponectin / Q000096:biosynthesis / Q000235:genetics; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000097:blood / Q000235:genetics
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D054419:Receptors, Adiponectin; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1