Characteristics of A20 gene polymorphisms in T-cell acute lymphocytic leukemia

Lihua Zhu, Fan Zhang, Qi Shen, Shaohua Chen, Xu Wang, Liang Wang, Lijian Yang, Xiuli Wu, Suming Huang, Christian A. Schmidt, Yangqiu Li

Research output: Contribution to journalArticle

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Abstract

A20 is a repressor of NF-κB and was recently shown to be frequently inactivated by deletions or mutations in several types of lymphomas including T-cell lymphoma. Little is known about the characteristics of A20 mutations in T-cell acute lymphoblastic leukemia (T-ALL). In this study, we analyzed A20 polymorphisms and characterized their features in 11 cases with T-ALL, 30 samples from healthy Chinese individuals, and 3 cells lines including CCRF-CEM, Molt-4, and Toledo cells. Two frequent A20 polymorphisms were found: a CCT deletion at position 12384 and a nucleotide exchange (A to C) at position 13751 (rs2307859 and rs661561). The homozygous form (CC) of rs661561 was detected in all 10 cases with detectable TALL, while only 80% (24/30) of the healthy controls had this genotype. We found one T-ALL case without the above frequent single-nucleotide polymorphisms (SNPs) in which a T to G mutation at position 12486 was found, which results in an amino acid exchange (Phe127Cys; rs2230926). Similar results were found in Molt-4 cells, which lack the frequent SNPs but have a heterozygous polymorphism at position 13749 (C > T) (rs5029948). Interestingly, the T-ALL case with the Phe127Cys mutation and Molt-4 cells demonstrated a high A20 copy number as measured by real-time polymerase chain reaction amplification with three primer sets that cover different regions of the A20 gene, corresponding to a high A20 and low NF-κB expression level. In conclusion, we characterized the features of A20 polymorphisms in T-ALL, and found that a low frequency A20 mutation, which was thought to be involved in malignant T-ALL development, might function differently in T cell lymphomas.

Original languageEnglish (US)
Pages (from-to)448-454
Number of pages7
JournalHematology
Volume19
Issue number8
DOIs
StatePublished - Dec 1 2014

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Genes
T-Cell Lymphoma
Mutation
Single Nucleotide Polymorphism
Sequence Deletion
Mutation Rate
Real-Time Polymerase Chain Reaction
Lymphoma
Nucleotides
Genotype
Amino Acids
Cell Line

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Zhu, L., Zhang, F., Shen, Q., Chen, S., Wang, X., Wang, L., ... Li, Y. (2014). Characteristics of A20 gene polymorphisms in T-cell acute lymphocytic leukemia. Hematology, 19(8), 448-454. https://doi.org/10.1179/1607845414Y.0000000160
Zhu, Lihua ; Zhang, Fan ; Shen, Qi ; Chen, Shaohua ; Wang, Xu ; Wang, Liang ; Yang, Lijian ; Wu, Xiuli ; Huang, Suming ; Schmidt, Christian A. ; Li, Yangqiu. / Characteristics of A20 gene polymorphisms in T-cell acute lymphocytic leukemia. In: Hematology. 2014 ; Vol. 19, No. 8. pp. 448-454.
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abstract = "A20 is a repressor of NF-κB and was recently shown to be frequently inactivated by deletions or mutations in several types of lymphomas including T-cell lymphoma. Little is known about the characteristics of A20 mutations in T-cell acute lymphoblastic leukemia (T-ALL). In this study, we analyzed A20 polymorphisms and characterized their features in 11 cases with T-ALL, 30 samples from healthy Chinese individuals, and 3 cells lines including CCRF-CEM, Molt-4, and Toledo cells. Two frequent A20 polymorphisms were found: a CCT deletion at position 12384 and a nucleotide exchange (A to C) at position 13751 (rs2307859 and rs661561). The homozygous form (CC) of rs661561 was detected in all 10 cases with detectable TALL, while only 80{\%} (24/30) of the healthy controls had this genotype. We found one T-ALL case without the above frequent single-nucleotide polymorphisms (SNPs) in which a T to G mutation at position 12486 was found, which results in an amino acid exchange (Phe127Cys; rs2230926). Similar results were found in Molt-4 cells, which lack the frequent SNPs but have a heterozygous polymorphism at position 13749 (C > T) (rs5029948). Interestingly, the T-ALL case with the Phe127Cys mutation and Molt-4 cells demonstrated a high A20 copy number as measured by real-time polymerase chain reaction amplification with three primer sets that cover different regions of the A20 gene, corresponding to a high A20 and low NF-κB expression level. In conclusion, we characterized the features of A20 polymorphisms in T-ALL, and found that a low frequency A20 mutation, which was thought to be involved in malignant T-ALL development, might function differently in T cell lymphomas.",
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Zhu, L, Zhang, F, Shen, Q, Chen, S, Wang, X, Wang, L, Yang, L, Wu, X, Huang, S, Schmidt, CA & Li, Y 2014, 'Characteristics of A20 gene polymorphisms in T-cell acute lymphocytic leukemia', Hematology, vol. 19, no. 8, pp. 448-454. https://doi.org/10.1179/1607845414Y.0000000160

Characteristics of A20 gene polymorphisms in T-cell acute lymphocytic leukemia. / Zhu, Lihua; Zhang, Fan; Shen, Qi; Chen, Shaohua; Wang, Xu; Wang, Liang; Yang, Lijian; Wu, Xiuli; Huang, Suming; Schmidt, Christian A.; Li, Yangqiu.

In: Hematology, Vol. 19, No. 8, 01.12.2014, p. 448-454.

Research output: Contribution to journalArticle

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AU - Zhu, Lihua

AU - Zhang, Fan

AU - Shen, Qi

AU - Chen, Shaohua

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