Characteristics of CARMA1-BCL10-MALT1-A20-NF-κB expression in T cell-acute lymphocytic leukemia.
Eur J Med Res
; 19: 62, 2014 Nov 11.
Article
em En
| MEDLINE
| ID: mdl-25384343
ABSTRACT
BACKGROUND:
Knowledge of the oncogenic signaling pathways of T-cell acute lymphoblastic leukemia (T-ALL) remains limited. Constitutive aberrant activation of the nuclear factor kappa B (NF-κB) signaling pathway has been detected in various lymphoid malignancies and plays a key role in the development of these carcinomas. The zinc finger-containing protein, A20, is a central regulator of multiple NF-κB-activating signaling cascades. A20 is frequently inactivated by deletions and/or mutations in several B-and T-cell lymphoma subtypes. However, few A20 mutations and polymorphisms have been reported in T-ALL. Thus, it is of interest to analyze the expression characteristics of A20 and its regulating factors, including upstream regulators and the CBM complex, which includes CARMA1, BCL10, and MALT1.METHODS:
The expression levels of CARMA1, BCL10, MALT1, A20, and NF-κB were detected in peripheral blood mononuclear cells (PBMCs) from 21 patients with newly diagnosed T-ALL using real-time PCR, and correlations between the aberrant expression of these genes in T-ALL was analyzed. Sixteen healthy individuals, including 10 males and 6 females, served as controls.RESULTS:
Significantly lower A20 expression was found in T-ALL patients (median 4.853) compared with healthy individuals (median 8.748; P = 0.017), and significantly increased expression levels of CARMA1 (median 2.916; P = 0.034), BCL10 (median 0.285; P = 0.033), and MALT1 (median 1.201; P = 0.010) were found in T-ALL compared with the healthy individuals (median 1.379, 0.169, and 0.677, respectively). In contrast, overexpression of NF-κB (median 0.714) was found in T-ALL compared with healthy individuals (median 0.335; P = 0.001). A negative correlation between the MALT1 and A20 expression levels and a positive correlation between CARMA1 and BCL10 were found in T-ALL and healthy individuals. However, no negative correlation was found between A20 and NF-κB and the MALT1 and NF-κB expression level in the T-ALL group.CONCLUSIONS:
We characterized the expression of the CARMA-BCL10-MALT1-A20-NF-κB pathway genes in T-ALL. Overexpression of CARMA-BCL10-MALT in T-ALL may contribute to the constitutive cleavage and inactivation of A20, which enhances NF-κB signaling and may be related to T-ALL pathogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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NF-kappa B
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Caspases
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
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Proteínas Adaptadoras de Sinalização CARD
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Guanilato Ciclase
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Proteínas de Neoplasias
Limite:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article