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Loss of promoter methylation contributes to the expression of functionally impaired PRDM1β isoform in diffuse large B-cell lymphoma

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Abstract

The positive regulatory domain I (PRDM1) is a transcriptional repressor that plays an important role in the B-cell differentiation. PRDM1β isoform is functionally impaired and overexpressed in a subset of diffuse large B-cell lymphoma with aggressive behavior. To investigate the possible epigenetic alteration on PRDM1β expression, methylation of PRDM1β promoter was assessed in B-lymphoma cell lines by bisulfite-sequencing PCR and screened in tumor samples of DLBCL patients using MassARRAY-quantitative methylation analysis. PRDM1β expression corresponded to promoter methylation status. CpG island of PRDM1β promoter possessed significant transcriptional activity, which could be modified by methylation. Loss of promoter methylation of PRDM1β was more frequently detected in lymphoma samples than in reactive hyperplasia. Thus, demethylation of abnormal tumor suppressor gene isoform might be linked to lymphoma progression.

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Acknowledgments

This work was supported by the Chinese National High Tech Program (863:2006AA02A301 and 863:2006AA02A405); the National Natural Science Foundation of China (30750335); the Shanghai Commission of Science and Technology (08410708800); the Shanghai Rising Star Program (09QH1401700); the Program for New Century Excellent Talents in University; the Fok Ying Tung Education Foundation (111035); “Shu Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation.

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Authors and Affiliations

  1. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China

    Yi-Wen Zhang, Hong-Qiang Xie, Yu Chen, Bo Jiao, Zhi-Xiang Shen, Sai-Juan Chen & Wei-Li Zhao

  2. Laboratory of Molecular Pathology, Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Shanghai, China

    Hong-Qiang Xie, Sai-Juan Chen & Wei-Li Zhao

Authors
  1. Yi-Wen Zhang
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  2. Hong-Qiang Xie
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  3. Yu Chen
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  4. Bo Jiao
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  5. Zhi-Xiang Shen
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  6. Sai-Juan Chen
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  7. Wei-Li Zhao
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Corresponding author

Correspondence to Wei-Li Zhao.

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Y.-W. Zhang, H.-Q. Xie and Y. Chen contributed equally to this manuscript.

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Zhang, YW., Xie, HQ., Chen, Y. et al. Loss of promoter methylation contributes to the expression of functionally impaired PRDM1β isoform in diffuse large B-cell lymphoma. Int J Hematol 92, 439–444 (2010). https://doi.org/10.1007/s12185-010-0689-3

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  • DOI: https://doi.org/10.1007/s12185-010-0689-3

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