期刊
DNA AND CELL BIOLOGY
卷 33, 期 1, 页码 49-56出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/dna.2013.2199
关键词
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资金
- National Natural Science Foundation of China [30871091, 91129720, 81270604]
- Ministry of Science and Technology [2012DFH30060]
- Fundamental Research Funds for the Central Universities [21610603, 21612116]
- Guangdong Science and Technology Project [2012B05060 0023]
- Training Programs of Innovation and Entrepreneurship for Undergraduates of Guangdong Province [1055912064]
Despite significant improvement in our understanding of T-cell acute lymphoblastic leukemia (T-ALL) biology and pathogenesis, many questions remain unanswered. In previous studies, we found a T-ALL case with two malignant T-cell clones with V1D2D3J1 and V2D3J2 rearrangements. In this study, we further characterized T-ALL cases with two malignant clones containing V1D3J1 and V2D1J1 rearrangements using fine-tiling array comparative genomic hybridization, ligation-mediated polymerase chain reaction (LM-PCR), sequencing, and reverse transcription polymerase chain reaction (RT-PCR) analysis. We further analyzed the distribution and clonality of the T-cell receptor (TCR) V and V subfamily T cells in the two T-ALL cases by RT-PCR and GeneScan. Monoclonal V1 and V2 subfamilies were confirmed in both samples, the V3 through V7 subfamilies could not be detected in the T-ALL samples, whereas the oligoclonal V8 subfamily could be identified. Based on the clinical finding that both of the T-ALL cases with two malignant T-cell clones had a poor outcome, we attempted to compare the expression pattern of genes related to T-cell activation and proliferation between cases with the malignant V1 and V2 T-cell clones and T-ALL cases with a mono-malignant V T-cell clone. We selected two T-ALL cases with VJ rearrangements and analyzed the expression level of Notch1, TAL1, and the CARMA-BCL10-MALT-A20-NF-B pathway genes by real-time PCR. A20 had significantly higher expression in the biclonal compared with the monoclonal T-ALL group (p=0.0354), and there was a trend toward higher expression for the other genes in the biclonal group with the exception of TAL1, although the differences were not statistically significant. In conclusion, we identified two T-ALL cases with biclonal malignant T-cell clones and described the characteristics of the biclonal T-ALL subtype and its gene expression pattern. Thus, our findings may improve the understanding of biclonal T-ALL.
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