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Myeloma and Plasma Cell Disease

Hypermethylation of p16INK4A gene promoter during the progression of plasma cell dyscrasia

Leukemia volume 15, pages 157–165 (2001)Cite this article

Abstract

Recent studies have indicated a close relationship between inactivation of tumor suppressor genes (TSGs) and disease progression. The genes encoding the cyclin-dependent kinase inhibitors p16INK4A and p15INK4B are potent TSGs, and correlations between their inactivation and disease progression have also been reported in various malignancies. In this study, we analyzed the methylation status of p16INK4Aand p15INK4B gene promoters in plasma cell dyscrasias (PCDs) by methylation-specific PCR (MSP). In analyses using DNAs extracted from bone marrow mononuclear cells (BM-MNCs), patients with multiple myeloma (MM) showed frequent hypermethylation of the p16INK4A gene (15/37, 41%), whereas p15INK4B gene methylation was not so frequent (5/37, 14%). Many patients whose BM-MNC showed dense methylation of the p16INK4A gene had extramedullary plasmacytoma (extra-PC), and all available extra-PC samples showed alterations of the p16INK4A gene (4; dense methylation, 1; homozygous deletion). In contrast to MM, hypermethylation of the p16INK4A gene was significantly infrequent in indolent PCDs (2/22, 9%, P = 0.0055). The infrequency in indolent PCDs was also confirmed by analyses using DNAs extracted from BM smears (1/29, 3%). It is possible that hypermethylation of the p16INK4A gene promoter contributes to progression to aggressive MM from indolent PCD, especially to extra-PC development.

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Acknowledgements

We thank Dr A Ichikawa and Dr H Suzuki (Gifu Tajimi Prefectural Hospital), Dr K Kato and Mr H Yamada (Kouseiren Kamo Hospital), Dr T Shibata (Minani-Seikyo Hospital), Dr H Mizuno and Dr K Yamao (Cyukyo Hospital) for allowing us to examine clinical samples. We also thank Ms S Hatano and Ms K Kondo for their excellent technical assistance. This study was supported in part by Grants-in-Aid from the Ministry of Health and Welfare of Japan.

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  1. First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

    T Uchida, T Kinoshita, T Ohno, H Ohashi, H Nagai & H Saito

  2. Department of Hematology, Nagoya Daini Red Cross Hospital, Nagoya, Japan

    T Uchida

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Uchida, T., Kinoshita, T., Ohno, T. et al. Hypermethylation of p16INK4A gene promoter during the progression of plasma cell dyscrasia. Leukemia 15, 157–165 (2001). https://doi.org/10.1038/sj.leu.2401991

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