Abstract
CTLA-4 is a key factor in regulating and maintaining self tolerance, providing a negative signal to the T cell and thus limiting immune responses. Several polymorphisms within the CTLA-4 gene have been associated with an increased risk of developing autoimmune diseases and, very recently, with susceptibility to human cancer. Acute lymphoblastic leukemia is a clonal disorder of lymphoid progenitors representing the most frequent malignancy of childhood. Here, we show the presence at significantly elevated levels of a circulating soluble form of CTLA-4 in 70% of B-ALL pediatric patients with active disease, the positive correlation between the percentage of leukemic B lymphocytes and the amount of serum sCTLA-4, and the expression of sCTLA-4 transcript by B cells in patients. Finally, a correlation between CD1d expression (a negative prognostic marker) and the sCTLA-4 in B-ALL patients was observed. This suggests a possible role of this soluble molecule as a marker of progression or severity of the neoplastic disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD1d / genetics*
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B-Lymphocytes / metabolism*
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B-Lymphocytes / pathology
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Biomarkers, Tumor / genetics*
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CTLA-4 Antigen / blood
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CTLA-4 Antigen / genetics*
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Case-Control Studies
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Child
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Child, Preschool
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Female
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Gene Expression
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Humans
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Immunophenotyping
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Lymphocyte Count
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Male
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Polymorphism, Genetic
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / blood
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
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RNA, Messenger / genetics*
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Solubility
Substances
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Antigens, CD1d
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Biomarkers, Tumor
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CD1D protein, human
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CTLA-4 Antigen
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RNA, Messenger
Grants and funding
This work was supported by grants from Fondazione CARIGE and from Associazione “Davide Ciavattini” Onlus. Fondazione CARIGE as well as Associazione “Davide Ciavattini” Onlus had no involvement in study design, nor in the collection, analysis and interpretation of data, nor in the writing of the report and in the decision to submit the paper for publication.