文章：

治疗相关髓系肿瘤：基因与环境的碰撞

Therapy-related myeloid neoplasms: when genetics and environment collide

原文发布日期：2017-08-24

DOI: 10.1038/nrc.2017.60

类型: Review Article

开放获取: 否

要点：

1. Therapy-related myeloid neoplasms (t-MN) arise as a late effect of chemotherapy and/or radiation administered for a primary condition, often a malignant disease, solid organ transplant or autoimmune disease.
2. The majority of t-MN have high-risk cytogenetic features, and the prognosis for patients with t-MN is poor, with a 5-year survival of 10%.
3. Germline mutations in genes associated with an inherited predisposition to cancer have been identified in approximately 20% of patients with t-MN.
4. Chemotherapy and/or radiotherapy promotes clonal selection of pre-existing, mutant haematopoietic stem cells in addition to directly inducing leukaemogenic mutations.
5. The somatic mutations in t-MN are indistinguishable from those occurring in de novo acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS).
6. Large chromosomal deletions, such as del(5q) and del(7q), that occur in t-MN do not harbour a single, recessive tumour suppressor gene but instead are part of a contiguous gene syndrome (CGS). Moreover, the genes involved in CGSs on these chromosomes act by haploinsufficiency.
7. An aberrant bone marrow microenvironment directly contributes to the pathogenesis of t-MN.

要点翻译：

1. 治疗相关髓系肿瘤（t-MN）是作为原发性疾病（通常是恶性疾病、实体器官移植或自身免疫性疾病）接受化疗和/或放疗后出现的远期效应。
2. 大多数t-MN具有高危细胞遗传学特征，患者预后较差，5年生存率为10%。
3. 在约20%的t-MN患者中已鉴定出与遗传性癌症易感相关基因的胚系突变。
4. 化疗和/或放疗除了直接诱导致白血病突变外，还会促进预先存在的突变造血干细胞的克隆选择。
5. t-MN中的体细胞突变与原发性急性髓系白血病（AML）和骨髓增生异常综合征（MDS）中的突变无法区分。
6. t-MN中出现的巨大染色体缺失（如del(5q)和del(7q）并不包含单个隐性抑癌基因，而是连续基因综合征（CGS）的一部分。此外，这些染色体上CGS所涉基因通过单倍体不足机制发挥作用。
7. 异常的骨髓微环境直接参与了t-MN的发病机制。

英文摘要：

Therapy-related myeloid neoplasms (t-MN) arise as a late effect of chemotherapy and/or radiation administered for a primary condition, typically a malignant disease, solid organ transplant or autoimmune disease. Survival is measured in months, not years, making t-MN one of the most aggressive and lethal cancers. In this Review, we discuss recent developments that reframe our understanding of the genetic and environmental aetiology of t-MN. Emerging data are illuminating who is at highest risk of developing t-MN, why t-MN are chemoresistant and how we may use this information to treat and ultimately prevent this lethal disease.

摘要翻译： 

治疗相关髓系肿瘤（t-MN）是化疗和/或放疗用于原发疾病（通常为恶性肿瘤、实体器官移植或自身免疫病）后出现的晚期并发症。其生存期以月计而非年计，使t-MN成为最具侵袭性和致命性的癌症之一。本综述讨论最新进展，这些进展重塑了我们对t-MN遗传和环境病因的理解。新兴数据正揭示哪些人患t-MN风险最高、t-MN为何对化疗耐药，以及我们如何利用这些信息来治疗并最终预防这一致命疾病。

原文链接：

Therapy-related myeloid neoplasms: when genetics and environment collide