Cancer treatment and research
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Acute promyelocytic leukemia(APL) is characterized by the t(15;17) chromosomal translocation leading to the formation of the PML-RARalpha oncoprotein. This leukemia has attracted considerable interest in recent years, being the first in which therapies that specifically target the underlying molecular lesion, i.e., all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), leading to induction of differentiation and apoptosis have been successfully used in clinical practice. The advent of ATRA therapy has transformed APL from being a disease with a poor outlook to one of the most prognostically favorable subsets of acute myeloid leukemia. ⋯ This raises the possibility that some patients can be cured using differentiation therapies alone, without the need for chemotherapy, thereby potentially reducing treatment-related toxicity. It is clear that the success of such an approach is critically dependent upon molecular diagnostics and monitoring for minimal residual disease (MRD) to distinguish those patients who can potentially be cured with differentiation therapy from those requiring additional myelosuppressive agents. This represents an exciting new phase in the treatment of acute leukemia, highlighting the potential of molecularly targeted and MRD-directed therapies to achieve an individualized approach to patient management.
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Epigenetics refers to a stable, mitotically perpetuated regulatory mechanism of gene expression without an alteration of the coding sequence. Epigenetic mechanism include DNA methylation and histone tail modifications. Epigenetic regulation is part of physiologic development and becomes abnormal in neoplasia, where silencing of critical genes by DNA methylation or histone deacetylation can contribute to leukemogenesis as an alternative to deletion or loss-of-function mutation. ⋯ It is now clear that these epigenetic changes play a significant role in development and progression of AML, and thus constitute important targets of therapy. The aim of targeting epigenetic effector protein or "epigenetic therapy" is to reverse epigenetic silencing and reactive various genes to induce a therapeutic effect such as differentiation, growth arrest, or apoptosis. Recent clinical studies have shown the relative safety and efficacy of such epigenetic therapies.