In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia
In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia
复制标题
DOI：
10.1182/blood-2016-07-723148
复制
发表时间：
2017-03-23
期刊：
影响因子：
20.3
通讯作者：
Wiemels, Joseph L.
中科院分区：
文献类型：
--
作者：
Francis, Stephen Starko;Wallace, Amelia D.;Wiemels, Joseph L.
人们普遍怀疑，感染在急性淋巴细胞白血病（ALL）的发展中起着病原学作用，这是最常见的儿童癌症，在大多数情况下可证实是产前起源的疾病。我们调查了诊断时的感染情况，然后评估了ALL患儿出生时感染的时间，以及年龄、性别和种族匹配的对照组，以确定潜在的因果性初始感染。对预处理骨髓标本（127例ALL与对照组的38例急性髓系白血病）进行全面的非靶向病毒组和细菌分析，发现儿童ALL在诊断时普遍存在巨细胞病毒（CMV）感染，白血病原细胞中存在活跃的病毒转录，血清中存在完整的病毒粒子。新生儿血液样本筛查显示，ALL病例（n = 268）的子宫内巨细胞病毒感染率明显高于健康对照组（n = 270）（优势比[OR]， 3.71，可信区间[CI]， 1.56-7.92, P 5.0016）。与非西班牙裔白人（OR=52.10 CI=5 0.69-7.13）相比，西班牙裔白人的风险更明显（OR=55.90， CI=51.89-25.96）。这是首次研究表明先天性巨细胞病毒感染是儿童ALL的危险因素，在西班牙裔儿童中更为突出。进一步调查巨细胞病毒是否为ALL的病因是有必要的。
It is widely suspected, yet controversial, that infection plays an etiologic role in the development of acute lymphoblastic leukemia (ALL), the most common childhood cancer and a disease with a confirmed prenatal origin in most cases. We investigated infections at diagnosis and then assessed the timing of infection at birth in children with ALL and age, gender, and ethnicity matched controls to identify potential causal initiating infections. Comprehensive untargeted virome and bacterial analyses of pretreatment bone marrow specimens (n = 127 ALL in comparison with 38 acute myeloid leukemia cases in a comparison group) revealed prevalent cytomegalovirus (CMV) infection at diagnosis in childhood ALL, demonstrating active viral transcription in leukemia blasts as well as intact virions in serum. Screening of newborn blood samples revealed a significantly higher prevalence of in utero CMV infection in ALL cases (n = 268) than healthy controls (n = 270) (odds ratio [OR], 3.71, confidence interval [CI], 1.56-7.92, P 5.0016). Risk was more pronounced in Hispanics (OR=55.90, CI=51.89-25.96) than in non-Hispanic whites (OR=52.10 CI=5 0.69-7.13). This is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children. Further investigation of CMV as an etiologic agent for ALL is warranted.