Acute myeloid leukaemia
Acute myeloid leukaemia
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DOI：
10.1038/nrdp.2016.10
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发表时间：
2016-03-10
影响因子：
81.5
通讯作者：
Linch, David C.
中科院分区：
文献类型：
--
作者：
Khwaja, Asim;Bjorkholm, Magnus;Linch, David C.
急性髓性白血病（AML）是一种以原始造血干细胞或祖细胞克隆性增殖为特征的疾病。髓细胞分化异常导致未成熟恶性细胞增多，红细胞、血小板和白细胞分化减少。这种疾病发生在所有年龄，但主要发生在老年人（60岁）。急性髓性白血病通常表现为快速发作的症状，可归因于骨髓衰竭，如果不及时治疗，可能在几周或几个月内致命。AML的基因组格局已经确定，遗传不稳定并不常见，驱动突变的数量相对较少。参与表观遗传调控的基因突变是常见的，是白血病发生的早期事件。AML的亚分类依赖于血液和骨髓细胞的形态学和细胞遗传学，但现在正在纳入特定的突变分析。过去35年来，年轻患者治疗的改善主要是由于剂量增加和更好的支持性护理。异体造血干细胞移植可用于巩固那些复发风险高的患者的缓解。基于对疾病病理生理学的进一步了解，大量的新药物——包括那些针对特定生化途径和免疫治疗方法的药物——正在进行试验。这些进展为乐观提供了充分的理由，尽管死亡率仍然很高，尤其是老年患者。
Acute myeloid leukaemia (AML) is a disorder characterized by a clonal proliferation derived from primitive haematopoietic stem cells or progenitor cells. Abnormal differentiation of myeloid cells results in a high level of immature malignant cells and fewer differentiated red blood cells, platelets and white blood cells. The disease occurs at all ages, but predominantly occurs in older people (>60 years of age). AML typically presents with a rapid onset of symptoms that are attributable to bone marrow failure and may be fatal within weeks or months when left untreated. The genomic landscape of AML has been determined and genetic instability is infrequent with a relatively small number of driver mutations. Mutations in genes involved in epigenetic regulation are common and are early events in leukaemogenesis. The subclassification of AML has been dependent on the morphology and cytogenetics of blood and bone marrow cells, but specific mutational analysis is now being incorporated. Improvements in treatment in younger patients over the past 35 years has largely been due to dose escalation and better supportive care. Allogeneic haematopoietic stem cell transplantation may be used to consolidate remission in those patients who are deemed to be at high risk of relapse. A plethora of new agents-including those targeted at specific biochemical pathways and immunotherapeutic approaches-are now in trial based on improved understanding of disease pathophysiology. These advances provide good grounds for optimism, although mortality remains high especially in older patients.