Biojone Estefânia Rodrigues, Guido Bruna Cândido, Cavalcante Larissa Lemos Mendanha, Dos Santos Júnior Agenor de Castro Moreira, de Pontes Robéria Mendonça, Furtado Felipe Magalhães, Córdoba José Carlos, Magalhães Isis Maria Quezado, de Oliveira Diêgo Madureira, Camargo Ricardo
Oncology and Hematology Division, Children's Hospital of Brasília, Brasília, Brazil.
Laboratory of Translational Research, Children's Hospital of Brasília, Brasília, Brazil.
Front Pediatr. 2024 Dec 6;12:1505060. doi: 10.3389/fped.2024.1505060. eCollection 2024.
There is consistent evidence that may be a driver gene in B-ALL and that selected cases may benefit from the use of FLT3 inhibitors. Our study was conducted to evaluate the frequency and types of FLT3 mutations in pediatric patients with B-ALL, the relative expression of this gene, and their influence on clinical evolution.
We evaluated 156 children with B-ALL treated between July 2018 and September 2023. Screening for FLT3 mutations was performed using RFLP and fragment analysis, while FLT3 expression was assessed by qPCR.
-TKD and/or -JM-INDEL mutations were found in 8 patients (5.1%). We did not identify any ITD-type mutations. None of the patients with identified mutations presented recurrent rearrangements in B-ALL or alterations in the , , or genes, suggesting that mutation may serve as the driving mechanism for leukemia in these cases. Two (2/8) patients with mutations experienced disease relapse. Although we did not observe overexpression among patients with mutations, expression levels were higher in these patients compared to WT patients. Four -WT patients presented overexpression, defined as RQ > 10. mutations or overexpression were not associated with relapses or survival rates.
Our findings do not support the inclusion of as a routine marker in the risk stratification of B-ALL patients; nevertheless, FLT3 alterations may be relevant for guiding personalized treatment approaches in specific clinical contexts.
有一致的证据表明，FLT3可能是B淋巴细胞白血病（B-ALL）中的驱动基因，部分病例可能受益于FLT3抑制剂的使用。我们开展这项研究旨在评估小儿B-ALL患者中FLT3突变的频率和类型、该基因的相对表达情况及其对临床病程的影响。
我们评估了2018年7月至2023年9月期间接受治疗的156例小儿B-ALL患者。采用限制性片段长度多态性（RFLP）和片段分析进行FLT3突变筛查，同时通过定量聚合酶链反应（qPCR）评估FLT3表达。
在8例患者（5.1%）中发现了-TKD和/或-JM插入缺失突变。我们未发现任何内部串联重复（ITD）型突变。在已鉴定出FLT3突变的患者中，无一例在B-ALL中出现复发性重排或在BCR、ABL或TEL基因中发生改变，这表明在这些病例中FLT3突变可能是白血病的驱动机制。2例（2/8）发生FLT3突变的患者出现疾病复发。虽然我们在发生FLT3突变的患者中未观察到FLT-3过表达，但与野生型（WT）患者相比，这些患者的FLT3表达水平更高。4例FLT3-WT患者出现FLT3过表达，定义为相对定量（RQ）>10。FLT3突变或过表达与复发率或生存率无关。
我们的研究结果不支持将FLT3作为B-ALL患者风险分层的常规标志物；然而，在特定临床背景下，FLT3改变可能与指导个性化治疗方法相关。
