Epigenetic therapies in MDS and AML.
Epigenetic therapies in MDS and AML.
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DOI：
10.1007/978-1-4419-9967-2_13
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发表时间：
2013
影响因子：
--
通讯作者：
Gore, Steven D.
中科院分区：
文献类型：
--
作者：
Griffiths, Elizabeth A.;Gore, Steven D.
使用低剂量低甲基化药物治疗骨髓增生异常综合征（MDS）和继发性急性髓细胞白血病（AML）患者已产生显著影响。过去，这些疾病的治疗方法有限，选择接受治疗的患者要接受高毒性的住院化疗，这些化疗往往无效。在低甲基化药物（阿扎胞苷和地西他滨）时代，可为高级别MDS或AML伴多系发育不良的患者提供门诊、相对低毒性治疗的替代方案。尽管这些药物的CR（CR）率仍相对较低，为15- 20%，但更大比例的患者将在血红蛋白、血小板和中性粒细胞计数方面获得临床显著改善，同时保持良好的门诊生活质量。随着我们对azanu-cleotides临床经验的扩展，关于患者选择，最佳给药策略，最佳反应的潜伏期和疾病进展后的最佳治疗持续时间的问题仍然存在，但毫无疑问，对于一些患者，这些药物在一段时间内提供了几乎奇迹般的临床益处。正在进行的临床试验与常规治疗药物、其他表观遗传活性药物或骨髓移植联合使用，继续为骨髓疾病患者优化这些药物提供了希望。尽管这些药物已证实有效的机制仍存在一些争议，但认为活性源于诱导DNA低甲基化、直接DNA损伤或甚至可能是免疫调节;毫无疑问，它们已成为抗髓系肿瘤药物的永久组成部分。
The use of low dose hypomethylating agents for patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML) has had made a significant impact. In the past, therapies for these diseases were limited and patients who elected to receive treatment were subject to highly toxic, inpatient chemotherapeutics, which were often ineffective. In the era of hypomethy-lating agents (azacitidine and decitabine), a patient with high grade MDS or AML with multilineage dysplasia can be offered the alternative of outpatient, relatively low-toxicity therapy. Despite the fact that CR (CR) rates to such agents remain relatively low at 15–20%, a much larger percentage of patients will have clinically significant improvements in hemoglobin, platelet, and neutrophil counts while maintaining good outpatient quality of life. As our clinical experience with azanu-cleotides expands, questions regarding patient selection, optimal dosing strategy, latency to best response and optimal duration of therapy following disease progression remain, but there is no question that for some patients these agents offer, for a time, an almost miraculous clinical benefit. Ongoing clinical trials in combination and in sequence with conventional therapeutics, with other epigenetically active agents, or in conjunction with bone marrow transplantation continue to provide promise for optimization of these agents for patients with myeloid disease. Although the mechanism(s) responsible for the proven efficacy of these agents remain a matter of some controversy, activity is thought to stem from induction of DNA hypom-ethylation, direct DNA damage, or possibly even immune modulation; there is no question that they have become a permanent part of the armamentarium against myeloid neoplasms.
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影响因子：
20.3
作者：
Garcia-Manero, Guillermo;Kantarjian, Hagop M.;Issa, Jean-Pierre
通讯作者：
Issa, Jean-Pierre
影响因子：
6.2
作者：
Costa, Rubens;Abdulhaq, Haifaa;Lister, John
通讯作者：
Lister, John
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
2.7
作者：
Greenberg, PL
通讯作者：
Greenberg, PL
影响因子：
2.7
作者：
CONSTANTINIDES, PG;TAYLOR, SM;JONES, PA
通讯作者：
JONES, PA