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Eur J Cancer. 2009 May;45(7):1137-1145. doi: 10.1016/j.ejca.2009.03.001. Epub 2009 Apr 5.

Epigenetic therapies in haematological malignancies: searching for true targets.

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Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy.
European Institute of Oncology, Via Adamello 16, 20100 Milan, Italy; Department of Biomolecular Sciences and Biotechnologies, University of Milan, Via Celoria 26, 20100 Milan, Italy. Electronic address:


Epigenetic alterations complement genetic mutations as a molecular mechanism leading to cell transformation, and maintenance of the cancer phenotype. Of note, they are reversible by pharmacological manipulation of the enzymes responsible for chromatin modification: indeed, epigenetic drugs (histone deacetylase inhibitors and DNA demethylating agents) are currently on the market, inducing proliferative arrest and death of tumor cells. These drugs, however, have been effective only in a few tumor types: the lack of consistent clinical results is mainly due to their use in a poorly targeted approach, since the epigenetic alterations present in cancer cells are mostly unknown. In a few cases (notably, leukemias expressing RAR and MLL fusion proteins), the molecular mechanisms underlying tumor-selective and tumor-specific epigenetic alterations have started to be deciphered. These studies are revealing a dazzling complexity in the mechanisms leading to alterations of the epigenome, and the need of combination therapies targeting different chromatin modifiers to reach an effective reversion of epigenetic alterations.

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