Abstract
To elucidate the characteristics of T-cell receptor (TCR) signal transduction in T-cells from acute myeloid leukemia (AML), the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20, NF-κB and MALT1-V1 gene expression levels in CD3+ T cells sorted from the peripheral blood of patients with AML were analyzed by real-time PCR. A significantly lower MALT1 and A20 expression level was found in T cells from patients with AML compared with healthy controls (p = 0.045, p < 0.0001); however, the expression level of MALT1-V1 (variant 1) was significantly higher in the AML group than in the healthy control group (p = 0.006), and the expression level of NF-κB was increased in the AML group. In conclusion, the characteristics of the expression pattern of MALT1-A20-NF-κB and the distribution of MALT1 variants in T cells from AML were first characterized. Overall, low TCR-CD3 signaling is related to low MALT1 expression, which may related to T cell immunodeficiency, while the up-regulation of MALT1-V1 may play a role in overcoming the T cell activity by downregulating A20 in patients with AML, which may be related to a specific response to AML-associated antigens.
Highlights
Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults, and its incidence is expected to further increase as the population ages
Based on our previous finding of low CD3 gene expression in T cells from patients with AML, in this study, we analyzed the expression level of the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20 and nuclear factor-κB (NF-κB) genes and found that an alternative expression pattern for these genes may be related to T cell dysfunction in AML
To investigate the downstream gene expression characteristics of the T-cell receptor (TCR)-CD3 pathway, the expression level of the MALT1, A20 and NF-κB genes was determined in the same CD3+ T cell samples by real-time PCR
Summary
Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults, and its incidence is expected to further increase as the population ages. The therapeutic value of donor lymphocyte infusions (DLI) in patients who relapse with AML is limited by a low efficacy and a high risk of GVHD. All of these attribute to the T cell mmunodeficiency. TCR and BCR triggering leads to the activation of the serinethreonine kinases PKC-θ and PKC-β, respectively, which subsequently phosphorylate the caspase-recruitment domain (CARD)–containing membrane-associated guanylate kinase protein 1 (CARMA1; called CARD11) [22] This phosphorylation event facilitates the recruitment of the CARD containing adaptor protein B-cell lymphoma 10 (Bcl-10) and the paracaspase mucosa-associated-lymphoidtissue lymphoma-translocation gene 1 (MALT1), resulting in assembly of the CARMA1–Bcl-10–MALT1 (CBM) complex. Based on our previous finding of low CD3 gene expression in T cells from patients with AML, in this study, we analyzed the expression level of the MALT1, A20 and NF-κB genes and found that an alternative expression pattern for these genes may be related to T cell dysfunction in AML
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