TY - JOUR
T1 - Decitabine and its role in the treatment of hematopoietic malignancies
AU - Plimack, Elizabeth R.
AU - Kantarjian, Hagop M.
AU - Issa, Jean Pierre
PY - 2007/8
Y1 - 2007/8
N2 - DNA methylation is responsible for abnormal silencing of many genes, including tumor suppressor genes, in cancer. Decitabine, an S-phase specific inhibitor of DNA methyltransferase, has been shown to decrease levels of abnormal methylation in neoplasia. Though initially investigated at high doses as a cytotoxic agent, recent studies show that when administered at low doses, the hypomethylating activity of decitabine is increased with a demonstrated increase in activity in hematopoietic malignancies. Multiple clinical trials, both in the United States and in Europe, have demonstrated the efficacy of decitabine in acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndrome (MDS). Recently approved by the United States Food and Drug Administration for the treatment of (MDS), decitabine represents an effective and well-tolerated therapeutic option in this disease, for which treatment options were previously scarce. While the activity in MDS is promising, primary and secondary resistance remain a problem. Investigations of combinations of decitabine with other agents, including histone deacetylase inhibitors, are currently ongoing in the hope of substantially prolonging survival in patients with hematologic malignancies.
AB - DNA methylation is responsible for abnormal silencing of many genes, including tumor suppressor genes, in cancer. Decitabine, an S-phase specific inhibitor of DNA methyltransferase, has been shown to decrease levels of abnormal methylation in neoplasia. Though initially investigated at high doses as a cytotoxic agent, recent studies show that when administered at low doses, the hypomethylating activity of decitabine is increased with a demonstrated increase in activity in hematopoietic malignancies. Multiple clinical trials, both in the United States and in Europe, have demonstrated the efficacy of decitabine in acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndrome (MDS). Recently approved by the United States Food and Drug Administration for the treatment of (MDS), decitabine represents an effective and well-tolerated therapeutic option in this disease, for which treatment options were previously scarce. While the activity in MDS is promising, primary and secondary resistance remain a problem. Investigations of combinations of decitabine with other agents, including histone deacetylase inhibitors, are currently ongoing in the hope of substantially prolonging survival in patients with hematologic malignancies.
KW - AML
KW - Decitabine
KW - Epigenetics
KW - MDS
KW - Methylation
UR - http://www.scopus.com/inward/record.url?scp=34547989446&partnerID=8YFLogxK
U2 - 10.1080/10428190701471981
DO - 10.1080/10428190701471981
M3 - Review article
C2 - 17701577
AN - SCOPUS:34547989446
SN - 1042-8194
VL - 48
SP - 1472
EP - 1481
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -