Characteristics of CARMA1-BCL10-MALT1-A20-NF-κB expression in T cell-acute lymphocytic leukemia.
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.
Yu
Y
Ma
Ziwei
Z
Liao
Yi
Y
Xu
Ziyun
Z
Zhong
Xu
X
Wang
Fan
F
Zhang
Shaohua
S
Chen
Lijian
L
Yang
Gengxin
G
Luo
Xin
X
Huang
Suming
S
Huang
Institute of Hematology, Jinan University, Guangzhou 510632, China. siulier@163.com.
Xiuli
X
Wu
Yangqiu
Y
Li
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006162:Guanylate Cyclase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009154:Mutation; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000473:pathology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; C426242:CARD11 protein, human; D006162:Guanylate Cyclase