The Prenatal Origin of Childhood Leukemia: Potential Applications for Epidemiology and Newborn Screening.
The Prenatal Origin of Childhood Leukemia: Potential Applications for Epidemiology and Newborn Screening.
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DOI：
10.3389/fped.2021.639479
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发表时间：
2021
影响因子：
2.6
通讯作者：
Nelson HH
中科院分区：
文献类型：
--
作者：
Marcotte EL;Spector LG;Mendes-de-Almeida DP;Nelson HH
儿童白血病是一种异质性疾病，在世界范围内发病率差异很大。作为循环肿瘤，儿童急性白血病是唯一可接近的，其自然史比实体瘤描述得更详细。几十年来，很明显，大多数儿童急性淋巴细胞白血病（ALL）和急性髓性白血病（AML）在子宫内发病。支持这一论点的间接证据包括发病年龄小和同卵双胞胎的高一致性。“回溯”白血病体细胞突变，特别是基因易位，到围产期收集的脐带血和干血斑点，提供了产前白血病发生的分子证据。通过容易获得的出生样本（如干燥的血斑）来检测患者的白血病易位，只要知道它们的特殊断点，就很容易。然而，要将这些发现转化为基于人群的筛查和白血病预防，需要能够在低频率细胞中检测所有可能断点的易位的新方法。一些研究试图在健康儿童的脐带血样本中筛查白血病易位，主要是常见的ETV6-RUNX1易位。大多数研究报告在健康儿童中发现了易位，但对患病率的估计差异很大，并且大大超过了白血病的发病率，这导致人们担心技术上的人为人为地夸大了出生时易位的患病率。新一代技术在出生时捕捉到这些易位的存在，有可能极大地增加我们对急性白血病流行病学的理解。例如，如果出生时出现白血病易位的儿童比例远远高于最终发展为急性白血病的儿童比例，那么导致疾病的暴露和体细胞分子事件是什么？出生时就有易位的孩子能成为预防疾病的目标吗？这些问题必须在大规模新生儿白血病筛查作为一项公共卫生倡议之前得到回答。在这里，我们回顾了关于急性白血病回溯和出生时白血病易位的患病率的文献。我们进一步建议使用新工具进行流行病学研究，以筛查白血病易位。
Childhood leukemias are heterogeneous diseases with widely differing incident rates worldwide. As circulating tumors, childhood acute leukemias are uniquely accessible, and their natural history has been described in greater detail than for solid tumors. For several decades, it has been apparent that most cases of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) initiate in utero. Circumstantial evidence in support of this contention includes the young age of onset and high rate of concordance among identical twins. “Backtracking” of leukemic somatic mutations, particularly gene translocations, to cord blood and dried blood spots collected during the perinatal period has provided molecular proof of prenatal leukemogenesis. Detection of a patient's leukemia translocation in easily accessible birth samples, such as dried blood spots, is straightforward with the knowledge of their idiosyncratic breakpoints. However, to translate these findings into population-based screening and leukemia prevention requires novel methods able to detect translocations at all possible breakpoints when present in a low frequency of cells. Several studies have attempted to screen for leukemic translocations, mainly the common ETV6-RUNX1 translocation, in cord blood samples from healthy children. Most studies have reported finding translocations in healthy children, but estimates of prevalence have varied widely and greatly exceed the incidence of leukemia, leading to concerns that technical artifact or contamination produced an artificially inflated estimate of translocation prevalence at birth. New generation techniques that capture the presence of these translocations at birth have the potential to vastly increase our understanding of the epidemiology of acute leukemias. For instance, if leukemic translocations are present at birth in a far higher proportion of children than eventually develop acute leukemia, what are the exposures and somatic molecular events that lead to disease? And could children with translocations present at birth be targeted for prevention of disease? These questions must be answered before large-scale newborn screening for leukemia can occur as a public health initiative. Here, we review the literature regarding backtracking of acute leukemias and the prevalence of leukemic translocations at birth. We further suggest an agenda for epidemiologic research using new tools for population screening of leukemic translocations.
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影响因子：
11.4
作者：
Chen, B.;Wang, Y-Y;Chen, S-J
通讯作者：
Chen, S-J
儿童 AML 的产前起源比儿童 ALL 的发生率要低。
影响因子：
3.8
作者：
Burjanivova T;Madzo J;Muzikova K;Meyer C;Schneider B;Votava F;Marschalek R;Stary J;Trka J;Zuna J
通讯作者：
Zuna J
影响因子：
3.7
作者：
Fueller E;Schaefer D;Fischer U;Krell PF;Stanulla M;Borkhardt A;Slany RK
通讯作者：
Slany RK
影响因子：
11.4
作者：
Enciso-Mora, V.;Hosking, F. J.;Houlston, R. S.
通讯作者：
Houlston, R. S.
影响因子：
6.4
作者：
Caughey, Robert W.;Michels, Karin B.
通讯作者：
Michels, Karin B.