儿童 B 细胞前体急性淋巴细胞白血病 (BCP-ALL) 可以通过白血病克隆特异性免疫球蛋白重链 (IGH) 重排追溯到出生时，这意味着这种疾病的产前起源。我们回顾性分析了新生儿血斑（Guthrie 卡） 24 名年龄为 1-9.6 岁（中位数 3.1 岁）的儿童 BCP-ALL 患者，在诊断骨髓样本中发现克隆型 IGH 重排。根据IGH重排序列，为每位患者设计2个患者特异性引物，用于半巢式聚合酶链反应检测出生时白血病前期克隆。54.2%的患者新生儿血斑中检测到克隆型IGH重排（13/24）。在诊断时检测到双重 IGH 重排的两例中，出生时仅存在一种重排，而在第三例中，在新生儿血液中检测到两种白血病重排。 ≤5 岁儿童的 Guthrie 卡阳性结果明显高于年龄较大的儿童 (p=0.011)。关于患者出生时和诊断时的特征，Guthrie 卡阳性与性别、出生体重和母亲年龄以及白细胞计数、骨髓母细胞百分比、免疫表型以及 ETV6/RUNX1 和 ETV6/RUNX1 的存在无关。诊断时的 TCF3/PBX1 融合基因。我们的研究证实，无论染色体畸变定义的分子亚型如何，很大一部分儿童 BCP-ALL 起源于子宫内。观察到的 Guthrie 卡阳性患者与 Guthrie 卡阴性患者的诊断年龄呈年轻趋势，这意味着诊断年龄取决于出生时白血病前期克隆的存在，以及出生后转化遗传事件的时间。© 2023 John威利

Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease.We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP-ALL aged 1-9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient-specific primers were designed for each patient and used in semi-nested polymerase chain reaction for the detection of preleukemic clones at birth.Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis.Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card-positive versus Guthrie card-negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events.© 2023 John Wiley & Sons Ltd.