Transient abnormal myelopoiesis (TAM) raises the risk for acute myeloid leukemia of Down syndrome (DS) (ML‐DS), and both are related to GATA1 pathogenic variants. Here, we analyzed which findings on complete blood count (CBC) are associated with TAM in a cohort of neonates with DS screened for GATA1 pathogenic variants. The CBCs were compared among 70 newborns with DS, including 16 patients (22.9%) with TAM (cases), and 54 patients (77.1%) without TAM (controls). TAM was defined as peripheral circulating blasts (PCBs) ≥ 1%. PCR and direct sequencing were used to screen DNA samples from peripheral blood for GATA1 exon 2 mutations. Multivariate logistic regression analyses determined that the mean count of lymphocytes was significantly higher in DS infants with TAM (p = .035) and that lymphocytosis confers a risk for TAM (adjusted odds ratio = 7.23, 95% confidence intervals: 2.02–25.92). Pathogenic variants of GATA1 were identified in 2 of 70 analyzed DS neonates (2.9%), of which one had ML‐DS and another had an asymptomatic TAM. Among those DS infants with TAM, the GATA1 pathogenic variant detection was 12.5%. Our results indicated that lymphocytosis is associated with TAM in neonates with DS. However, since not all infants with an abnormal CBC had TAM, and not all infants with TAM had GATA1 pathogenic variants, we emphasize that only the search for GATA1 pathogenic variants allows the proper identification of the subgroup of DS infants with a real increasing in risk for ML‐DS.

中文翻译：

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在筛查GATA1致病变异的一过性唐突综合症新生儿中，有短暂性异常骨髓生成​​的全血细胞计数差异。

短暂性异常骨髓生成​​（TAM）增加了唐氏综合症（DS）（ML-DS）的急性髓性白血病的风险，并且两者均与GATA1致病变异有关。在这里，我们分析了DS筛选GATA1致病性变体的新生儿队列中哪些与全血细胞计数（CBC）有关的发现与TAM相关。在70名患有DS的新生儿中比较了CBC，包括16名TAM患儿（22.9％）和54名TAM患儿（77.1％）（对照组）。TAM被定义为≥1％的外周循环冲击波（PCB）。PCR和直接测序用于从外周血DNA样品中筛选GATA1外显子2突变。多因素logistic回归分析确定患有DSM的DS婴儿的淋巴细胞平均计数显着更高（p = .035），并且淋巴细胞增多会导致发生TAM的风险（校正比值比= 7.23，95％置信区间：2.02–25.92）。在70例经分析的DS新生儿中，有2例（2.9％）鉴定出GATA1的致病变异，其中一个患有ML-DS，另一个患有无症状的TAM。在那些患有TAM的DS婴儿中，GATA1致病变异检测率为12.5％。我们的结果表明，DS新生儿中淋巴细胞增多与TAM相关。但是，由于并非所有CBC异常的婴儿都有TAM，也不是所有TAM婴儿都具有GATA1致病性变体，我们强调只有搜索GATA1致病性变体才能正确鉴定DS婴儿的亚组，从而真正增加ML-DS的风险。