Orozco-Vela Mireya, Corona-Rivera Alfredo, Cruz-Osorio Rosa Margarita, Mendoza-Maldonado Lucero, Márquez-Mora Aurea, Barba-Barba César Cenobio, Peña-Padilla Christian, Baldomero-López Alejandra, Bobadilla-Morales Lucina, Corona-Rivera Jorge Román
University of Guadalajara, Health Sciences University Center, Department of Molecular Biology and Genomics, 'Dr. Enrique Corona Rivera' Institute of Human Genetics, Guadalajara, Jalisco, Mexico.
'Dr. Juan I. Menchaca' Civil Hospital of Guadalajara, Division of Pediatrics and Paramedic and Auxiliary Diagnostic Services, Service of Hematology-Oncology, Cytogenetics Unit, Guadalajara, Jalisco, Mexico.
Am J Med Genet A. 2020 Sep;182(9):2085-2093. doi: 10.1002/ajmg.a.61748. Epub 2020 Jul 18.
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.
短暂性异常髓系造血（TAM）会增加唐氏综合征（DS）相关急性髓系白血病（ML-DS）的发病风险，且二者均与GATA1致病变异有关。在此，我们分析了在一组筛查GATA1致病变异的DS新生儿队列中，全血细胞计数（CBC）的哪些结果与TAM相关。对70例DS新生儿的CBC进行了比较，其中包括16例（22.9%）患有TAM的患者（病例组）和54例（77.1%）未患TAM的患者（对照组）。TAM定义为外周循环原始细胞（PCB）≥1%。采用聚合酶链反应（PCR）和直接测序法对外周血DNA样本进行GATA1外显子2突变筛查。多因素逻辑回归分析确定，患有TAM的DS婴儿淋巴细胞平均计数显著更高（p = 0.035），且淋巴细胞增多会增加患TAM的风险（调整优势比 = 7.23，95%置信区间：2.02 - 25.92）。在70例分析的DS新生儿中有2例（2.9%）鉴定出GATA1致病变异，其中1例患有ML-DS，另1例患有无症状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，淋巴细胞增多与DS新生儿的TAM相关。然而，由于并非所有CBC异常的婴儿都患有TAM，且并非所有患有TAM的婴儿都有GATA1致病变异，我们强调只有寻找GATA1致病变异才能正确识别出ML-DS发病风险真正增加的DS婴儿亚组。
