Associations between early-life and in utero infections and cytomegalovirus-positive acute lymphoblastic leukemia in children.
Associations between early-life and in utero infections and cytomegalovirus-positive acute lymphoblastic leukemia in children.
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DOI：
10.1002/ijc.34292
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发表时间：
2023-03-01
影响因子：
6.4
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中科院分区：
文献类型：
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儿童感染和巨细胞病毒（CMV）与儿童急性淋巴细胞白血病（ALL）相关。CMV使宿主免疫系统失调并改变对随后抗原暴露的免疫应答。我们怀疑这种免疫失调导致儿童期症状性感染的数量增加，从而允许白血病前克隆的扩增。我们探讨了儿童感染、妊娠期母体感染和CMV阳性ALL之间的关系。使用液滴数字PCR检测，我们筛选了来自加州儿童白血病研究（1995 - 2015）的诊断性ALL骨髓样本中是否存在CMV DNA，以识别CMV阳性和CMV阴性病例。我们进行了一项仅病例分析（n = 524），使用logistic回归比较CMV阳性和CMV阴性ALL病例之间儿童感染和妊娠期间母体感染的数量和类型。随着出生后前12个月内感染数量的增加，儿童在诊断时更有可能归类为骨髓中CMV DNA的最高三分位数（OR：1.04，95% CI：1.01 - 1.08）。具体而言，在前12个月内报告咳嗽或流感的患者在ALL诊断时更有可能为CMV阳性（OR：2.15，95% CI：1.06 - 4.37和OR：2.06，95% CI：1.17 - 3.63）。此外，妊娠期间有母体感染史的患者更可能为CMV阳性（OR：2.12，95% CI：1.24 - 3.62）。我们假设存在潜在免疫失调的儿童在儿童期发生更多症状性感染，最终为CMV阳性ALL;这种潜在免疫失调可能是由于CMV暴露（子宫内或婴儿早期）导致的早期免疫系统改变，表明CMV和ALL病因之间存在潜在联系。 有什么新消息吗？ 由于巨细胞病毒（CMV）诱导的免疫功能改变，生命早期的巨细胞病毒（CMV）感染可能导致儿童急性淋巴细胞白血病（ALL）的发生。在本研究中，在参加加州儿童白血病研究的ALL儿童中，研究了儿童ALL风险与宫内或早期CMV暴露之间的关系。仅病例分析显示，在妊娠期间暴露于母体感染的儿童比CMV阴性ALL更有可能患有CMV阳性ALL。在生命早期感染次数增加的儿童在ALL诊断时更有可能是CMV阳性。
Childhood infections and cytomegalovirus (CMV) are associated with pediatric acute lymphoblastic leukemia (ALL). CMV dysregulates the host immune system and alters the immune response to subsequent antigenic exposures. We suspect that this immune dysregulation contributes to increased numbers of symptomatic infections in childhood allowing for expansion of pre‐leukemic clones. We explored the association between childhood infections, maternal infections during pregnancy and CMV‐positive ALL. Using a droplet digital PCR assay, we screened diagnostic ALL bone marrow samples from the California Childhood Leukemia Study (1995‐2015) for the presence of CMV DNA identifying CMV‐positive and CMV‐negative cases. We performed a case‐only analysis (n = 524) comparing the number and types of childhood infections and maternal infections during pregnancy between CMV‐positive and CMV‐negative ALL cases using logistic regression. With increasing numbers of infections in the first 12 months of life, children were more likely to classify to the highest tertile of CMV DNA in the bone marrow at diagnosis (OR: 1.04, 95% CI: 1.01‐1.08). Specifically, those reporting cough or flu in the first 12 months were more likely to be CMV‐positive at ALL diagnosis (OR: 2.15, 95% CI: 1.06‐4.37 and OR: 2.06, 95% CI: 1.17‐3.63 respectively). Furthermore, those with a history of maternal infection during pregnancy were more likely to be CMV‐positive (OR: 2.12, 95% CI: 1.24‐3.62). We hypothesize that children with underlying immune dysregulation develop more symptomatic infections in childhood and ultimately CMV‐positive ALL; this underlying immune dysregulation may be due to early immune system alterations via CMV exposure (in utero or early infancy) proposing a potential link between CMV and ALL etiology. What's new? Cytomegalovirus (CMV) infection early in life likely contributes to the development of childhood acute lymphoblastic leukemia (ALL), owing to CMV‐induced alterations in immune function. In the present study, the relationship between risk of childhood ALL and exposure to CMV in utero or early life was investigated among children with ALL who participated in the California Childhood Leukemia Study. Case‐only analysis shows that children exposed to maternal infections during pregnancy are more likely to have CMV‐positive ALL than CMV‐negative ALL. Children with increased numbers of infections in early life are more likely to be CMV‐positive at the time of ALL diagnosis.
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影响因子：
105.7
作者：
Gilham, C;Peto, J;Alexander, FE
通讯作者：
Alexander, FE
影响因子：
17.1
作者：
Furman D;Jojic V;Sharma S;Shen-Orr SS;Angel CJ;Onengut-Gumuscu S;Kidd BA;Maecker HT;Concannon P;Dekker CL;Thomas PG;Davis MM
通讯作者：
Davis MM
影响因子：
--
作者：
Jenks, Carolyn M;Hoff, Stephen R;Mithal, Leena B
通讯作者：
Mithal, Leena B
影响因子：
11.2
作者：
de Smith AJ;Kaur M;Gonseth S;Endicott A;Selvin S;Zhang L;Roy R;Shao X;Hansen HM;Kang AY;Walsh KM;Dahl GV;McKean-Cowdin R;Metayer C;Wiemels JL
通讯作者：
Wiemels JL
影响因子：
168.9
作者：
Wiemels, JL;Cazzaniga, G;Greaves, MF
通讯作者：
Greaves, MF