大鼠肉瘤病毒(RAS)通路控制细胞增殖、分化和凋亡，这已与各种血液恶性肿瘤的发病机制有关。RAS基因突变在儿童急性淋巴细胞白血病（ALL）中相对频繁，其预后重要性一直存在争议。我们的目标是研究新诊断的93名ALL儿童中的RAS基因突变状况和预后。我们在中国儿童白血病组-急性淋巴细胞白血病2018(CCLG-ALL-2018)协议下，回顾性分析了93名ALL患儿在安徽省儿童医院接受第一次诱导化疗的临床特征、治疗和预后。所有基因组DNA样本均来自新诊断的骨髓单个核细胞。通过聚合酶链反应（PCR）进行RAS基因突变检测。所有孩子被分为标准、中等和高风险组，并根据CCLG-ALL-2018协议的风险治疗方案进行治疗。 在93个ALL儿童中，有26个（27.9％）RAS突变呈阳性，其中19个为N-RAS突变，8个为K-RAS突变，1个为双重突变。ETV6/RUNX1融合基因是最常见的遗传改变（n=16, 17.2%）。第一次诱导化疗期间最常见的不良事件是凝血异常（n=76, 81.7％），其次是发热（n=71, 76.3％）和丙氨酸转氨酶(ALT)升高（n=34, 36.6%）。与RAS突变阴性组相比，RAS突变组的高胆红素血症风险显着降低（P=0.018），在其他任何不良事件方面没有显着差异。第一次诱导化疗期间粒细胞完全减少的平均持续时间为6天，RAS突变组和RAS阴性组的平均持续时间分别为6天和5天，没有显着差异。多元线性回归分析显示，在RAS突变组中，当体重指数（BMI）超过所有ALL患儿的中位数（BMI>15.38）时，粒细胞完全减少的风险显着增加（P=0.003）。 在RAS突变的儿童中，新诊断的ALL与融合基因表达的相关性较小。RAS突变增加了第一次诱导化疗期间粒细胞完全减少的风险，降低BMI并减少ALL儿童的高胆红素血症的风险。

The rat sarcoma virus (RAS) pathway controls cell proliferation, differentiation, and apoptosis, which have been implicated in the pathogenesis of various hematological malignancies. Prognostic importance of RAS gene mutation, relatively frequently in childhood acute lymphoblastic leukemia (ALL), has been debated. We aimed to study RAS gene mutation profile and prognosis in 93 children with newly diagnosed ALL.We retrospectively analyzed clinical characteristics, treatment, and outcomes of 93 ALL children during first induction chemotherapy in Anhui Provincial Children's Hospital under the Chinese Children's Leukemia Group-acute lymphoblastic leukemia 2018 (CCLG-ALL-2018). All genomic DNA samples were obtained from bone marrow mononuclear cells upon new diagnosis. RAS gene mutation was performed by polymerase chain reaction (PCR). All children were stratified into standard-, medium-, and high-risk groups, and then treated with risk-based regimens according to CCLG-ALL-2018 protocol.Of 93 ALL children, 26 (27.9%) were positive for RAS mutation, among whom 19 had N-RAS mutation, 8 had K-RAS mutation, and 1 had a double mutation. The ETV6/RUNX1 fusion gene was the most common genetic alteration (n=16, 17.2%). The most common adverse events during first induction chemotherapy were coagulation abnormalities (n=76, 81.7%), followed by fever (n=71, 76.3%) and alanine transaminase (ALT) elevation (n=34, 36.6%). Compared with negative RAS mutation group, the risk of hyperbilirubinemia was significantly reduced in RAS mutation group (P=0.018), and there was no significant difference in any other adverse events. The average duration of agranulocytosis during first induction chemotherapy was 6 days, and the average duration of agranulocytosis in RAS mutation group and RAS negative group was 6 and 5 days, with no significant difference. Multivariate linear regression analysis showed that in RAS mutation group, when body mass index (BMI) exceeded the median value of this ALL population (BMI >15.38), the risk of agranulocytosis was significantly increased (P=0.003).Newly diagnosed ALL in children with RAS mutation is less likely to be associated with fusion gene expression. RAS mutation increases the risk of agranulocytosis duration during first induction chemotherapy, lowers BMI and reduces the risk of hyperbilirubinemia in ALL children.2023 Translational Pediatrics. All rights reserved.