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Thymic function and immunoglobulin mutation genotype in B‐cell chronic lymphocytic leukemia patients
Author(s) -
Nardini Elena,
Neri Francesca,
Vicenzi Elisa,
Poli Guido,
Capello Daniela,
Gaidano Gianluca,
Vitolo Umberto,
Ménard Sylvie,
Balsari Andrea
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11482
Subject(s) - somatic hypermutation , chronic lymphocytic leukemia , immunology , antibody , immune system , b cell , biology , peripheral blood mononuclear cell , leukemia , medicine , genetics , in vitro
Abstract B‐cell chronic lymphocytic leukemia (B‐CLL) is characterized by a profound dysregulation of the host's immune system at both the humoral and cellular level. We investigated to see if this dysregulation could be due partly to thymus dysfunction by quantifying the number of signal joint T‐cell receptor excision circles (sjTRECs) in peripheral blood mononuclear cells of 30 untreated B‐CLL patients at diagnosis and in age‐matched healthy controls. sjTRECs were found decreased, normal and elevated in 19, 9 and 2 patients, respectively, in comparison to age‐matched controls. We next speculated that sjTREC levels might be related to an accredited B‐CLL prognostic marker represented by the somatic hypermutation (SHM) status of the variable heavy chain (V H ) genes. Eight of 17 patients with SHMs had sjTREC levels in the range of or higher than normal donors, whereas only 3 of the 13 patients lacking SHMs had normal sjTREC levels. After a 5‐year observation period in 16 patients for whom a clinical follow‐up was available, only 2 of 10 patients with SHMs progressed vs. 5 of 6 patients without SHMs and 3 of 7 patients with normal or higher sjTREC levels progressed vs . 4 of 9 with low sjTREC levels. Our study demonstrates that sjTREC levels are decreased in >60% of B‐CLL patients and suggests a potential role of thymus in the immune dysfunction of these patients. © 2003 Wiley‐Liss, Inc.