DNA methylation is involved in malignancy and is seen, in progression, in more than 80% of all solid tumours. Methylation is one of the main physiological processes to induce silencing of gene expression. Much work has focused on the suppressor gene p16, which acts as a negative cell cycle regulator, while its inhibition (via methylation) will have a positive effect on the cell cycle advance. The methylation status of the p16 gene was analysed in a group of 159 patients. Methylation of the p16 gene was seen in 41/98 (42%) patients with multiple myeloma and 4/5 (80%) patients with primary plasma cell leukaemias. This data favours the importance of p16 methylation on cell cycle regulation in multiple myeloma. In a proposed mechanism, methylated CpG islands attract a protein, MeCP2, which recruits a transcriptional inhibitory complex that includes histone deacetylases. The deacetylated lysine tails of the histones closely interact with DNA, resulting in a transcriptionally repressed chromatin with inhibited gene transcription, providing potential synergy between demethylating drugs and histone deacetylase inhibitors. Based on the knowledge of epigenetic mechanisms, the potential application of demethylating agents should be further investigated. Multiple myeloma remains an incurable disease, so new treatment strategies are needed to improve the outcome of patients.

Herman JG, Graff JR, Myohanen S, et al: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 1996;93:9821–9826.
Galm O, Yoshikawa H, Esteller M, et al: SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Blood 2003;101:2784–2788.
Chim CS, Fung TK, Cheung WC, et al: SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic activation of the Jak/STAT pathway. Blood 2004;103:4630–4635.
Mateos MV, Garcia-Sanz R, Lopez-Perez R, et al: p16/INK4a gene inactivation by hypermethylation is associated with aggressive variants of monoclonal gammopathies. Hematol J 2001;2:146–149.
Mateos MV, Garcia-Sanz R, Lopez-Perez R, et al: Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival. Br J Haematol 2002;118:1034–1040.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.