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Promoter hypermethylation and global hypomethylation are independent epigenetic events in lymphoid leukemogenesis with opposing effects on clinical outcome

Leukemia volume 20, pages 1445–1447 (2006)Cite this article

Deregulation of the DNA-methylating machinery is associated with neoplastic transformation of many types of cells in humans. Both general genomic hypomethylation and regional hypermethylation coexist in DNA extracted from different types of neoplastic tissues. A number of studies have sought to reconcile this apparent paradox, suggesting that in solid cancers, the high frequency of DNA hypomethylation, the nature of the affected sequences and the absence of associations with DNA hypermethylation are consistent with an independent role of DNA undermethylation in the development of these solid neoplasms.1, 2

We have recently shown that the methylation of cytosine nucleotides in acute lymphoblastic leukemia (ALL) cells is the most important way to inactivate cancer-related genes in this disease. In fact, this epigenetic event can help to inactivate tumor-suppressive apoptotic or growth-arresting responses and has prognostic impact in B- and T-ALL.3, 4 The presence in individual tumors of multiple genes simultaneously methylated (a condition termed CpG island methylator phenotype or CIMP+) is an independent factor of poor prognosis in both childhood and adult ALL in terms of disease-free survival (DFS) and overall survival (OS). However, no studies have addressed the role of hypomethylation in lymphoid leukemogenesis and therefore, it is unclear whether these epigenetic changes are causally linked, or are distinct and biologically unrelated phenomena.

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Acknowledgements

This work was supported by Grants from Fondo de Investigacion Sanitaria (FIS, Spain) 03/0141, 01/0013-01, 01/F018, 02/1299; Navarra Goverment (31/2002); RETIC C03/10, Junta de Andalucia 03/143; 03/144 and funds from IMABIS (Malaga. Spain), ‘UTE project CIMA’, Fundación de Investigación Médica Mutua Madrileña Automovilista and Asociacion Medicina e Investigacion (AMI).

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Authors and Affiliations

  1. Hematology Department, Reina Sofia Hospital, Cordoba, Spain

    J Roman-Gomez, J A Castillejo & A Torres

  2. Hematology Department, Carlos Haya Hospital, Malaga, Spain

    A Jimenez-Velasco, G Navarro, M Barrios & A Heiniger

  3. Hematology Department, Cellular Therapy Area, Clinica Universitaria/School of Medicine, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain

    X Agirre, L Garate, E San Jose-Eneriz, L Cordeu & F Prosper

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Roman-Gomez, J., Jimenez-Velasco, A., Agirre, X. et al. Promoter hypermethylation and global hypomethylation are independent epigenetic events in lymphoid leukemogenesis with opposing effects on clinical outcome. Leukemia 20, 1445–1447 (2006). https://doi.org/10.1038/sj.leu.2404257

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