TY - CHAP
T1 - Epigenetic mechanisms in AML - A target for therapy
AU - Oki, Yasuhiro
AU - Issa, Jean Pierre J.
PY - 2010
Y1 - 2010
N2 - Epigenetics refers to a stable, mitotically perpetuated regulatory mechanism of gene expression without an alteration of the coding sequence. Epigenetic mechanisms 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. In acute myelogenous leukemia (AML), aberrant DNA methylation can be observed in multiple functionally relevant genes such as p15, p73, E-cadherin, ID4, RARβ2. Abnormal activities of histone tail-modifying enzymes have also been seen in AML, frequently as a direct result of chromosomal translocations. 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 reactivate 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.
AB - Epigenetics refers to a stable, mitotically perpetuated regulatory mechanism of gene expression without an alteration of the coding sequence. Epigenetic mechanisms 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. In acute myelogenous leukemia (AML), aberrant DNA methylation can be observed in multiple functionally relevant genes such as p15, p73, E-cadherin, ID4, RARβ2. Abnormal activities of histone tail-modifying enzymes have also been seen in AML, frequently as a direct result of chromosomal translocations. 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 reactivate 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.
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U2 - 10.1007/978-0-387-69259-3_2
DO - 10.1007/978-0-387-69259-3_2
M3 - Chapter
C2 - 20306243
AN - SCOPUS:77956163003
SN - 9780387692579
T3 - Cancer Treatment and Research
SP - 19
EP - 40
BT - Acute Myelogenous Leukemia
A2 - Nagarajan, Lalitha
ER -