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Characteristics of CARMA1-BCL10-MALT1-A20-NF-kappaB expression in T cell-acute lymphocytic leukemia.

Authors: Ma, Y  Liao, Z  Xu, Y  Zhong, Z  Wang, X  Zhang, F  Chen, S  Yang, L  Luo, G  Huang, X  Huang, S  Wu, X  Li, Y 
Citation: Ma Y, etal., Eur J Med Res. 2014 Nov 11;19:62. doi: 10.1186/s40001-014-0062-8.
Pubmed: (View Article at PubMed) PMID:25384343
DOI: Full-text: DOI:10.1186/s40001-014-0062-8

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-kappaB) 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-kappaB-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-kappaB 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-kappaB (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-kappaB and the MALT1 and NF-kappaB expression level in the T-ALL group. CONCLUSIONS: We characterized the expression of the CARMA-BCL10-MALT1-A20-NF-kappaB 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-kappaB signaling and may be related to T-ALL pathogenesis.

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CRRD Object Information
CRRD ID: 11100039
Created: 2016-06-14
Species: All species
Last Modified: 2016-06-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.