Garcia-Solorio Joaquin, Núñez-Enriquez Juan Carlos, Jiménez-Olivares Marco, Flores-Lujano Janet, Flores-Espino Fernanda, Molina-Garay Carolina, Cervera Alejandra, Casique-Aguirre Diana, Peñaloza-Gonzalez José Gabriel, Baños-Lara Ma Del Rocío, García-Soto Ángel, Galván-Díaz César Alejandro, Olaya-Vargas Alberto, Aguilar Hilario Flores, Mata-Rocha Minerva, Garrido-Hernández Miguel Ángel, Solís-Poblano Juan Carlos, Luna-Silva Nuria Citlalli, Cano-Cuapio Lena Sarahi, Aristil-Chery Pierre Mitchel, Herrera-Quezada Fernando, Carrillo-Sanchez Karol, Muñoz-Rivas Anallely, Flores-Lagunes Luis Leonardo, Mendoza-Caamal Elvia Cristina, Villegas-Torres Beatriz Eugenia, González-Osnaya Vincent, Jiménez-Hernández Elva, Torres-Nava José Refugio, Martín-Trejo Jorge Alfonso, Gutiérrez-Rivera María de Lourdes, Espinosa-Elizondo Rosa Martha, Merino-Pasaye Laura Elizabeth, Pérez-Saldívar María Luisa, Jiménez-Morales Silvia, Curiel-Quesada Everardo, Rosas-Vargas Haydeé, Mejía-Arangure Juan Manuel, Alaez-Verson Carmen
Laboratorio de Diagnóstico Genómico, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Unidad de Investigación Médica en Epidemiología Clínica, Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional (CMN) Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
Front Oncol. 2024 Apr 3;14:1337954. doi: 10.3389/fonc.2024.1337954. eCollection 2024.
Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. is a complex biomarker associated with a poor prognosis. It is characterized by deletion coexisting with , , or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the profile and the mutational spectrum of , and genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.
A total of 206 pediatric patients with B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.
We identified the profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (), a trend toward high-risk stratification (), and a decrease in 5-year Overall Survival (OS) () were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for (35.9%) and (35.9%) but lower for (26.6%). group was older at diagnosis (), and most of them were classified as high-risk (73.8%, ), while patients with had a higher leukocyte count () and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, ) than the non-mutated patients. A decrease in OS was found in and patients, but the significance was lost after was removed.
Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.
在儿童B细胞急性淋巴细胞白血病（B-ALL）中已鉴定出导致白血病发生的复发性基因改变，其中一些有助于完善分类、预后评估和治疗选择。是一种与预后不良相关的复杂生物标志物。其特征是缺失与、或PAR1区域缺失共存。在墨西哥儿童B-ALL患者中，这些改变的突变谱和临床影响几乎未被探索。在此，我们报告了谱系的频率以及、和基因的突变谱，并评估了它们对一组B-ALL患者总生存期（OS）的影响。
共纳入206例儿童B-ALL患者。在治疗开始前诊断时从骨髓样本中获取DNA。使用定制设计的二代测序 panel进行突变分析。采用Kaplan-Meier分析估计总生存期。
我们在21.8%的患者中鉴定出谱系，这一比例高于先前其他研究报道。观察到患者年龄显著更大（），有高危分层趋势（），5年总生存期（OS）降低（），尽管我们队列中不同的治疗方案会影响总生存期。发现（35.9%）和（35.9%）的突变频率高于报道，但（26.6%）的突变频率较低。组诊断时年龄更大（），且大多数被归类为高危（73.8%，），而有突变的患者白细胞计数更高（），原始细胞百分比有更高的趋势（98.6%，>50%原始细胞，），高于未突变患者。在和患者中发现总生存期降低，但在去除后这种显著性消失。
我们的研究结果表明，墨西哥B-ALL患者中与不良预后相关的遗传标志物患病率更高。将基因组方法纳入诊断过程，这在低收入和中等收入国家是一项重大的未满足需求，将有助于全面识别相关改变，改善疾病分类、治疗选择和总体预后。
