墨西哥儿童急性髓系白血病患者的突变图谱：预后意义
Mutational Landscape of in Mexican Pediatric Acute Myeloid Leukemia Patients: Prognostic Implications.
作者信息
Molina Garay Carolina, Carrillo Sánchez Karol, Flores Lagunes Luis Leonardo, Jiménez Olivares Marco, Muñoz Rivas Anallely, Villegas Torres Beatríz Eugenia, Flores Aguilar Hilario, Núñez Enríquez Juan Carlos, Jiménez Hernández Elva, Bekker Méndez Vilma Carolina, Torres Nava José Refugio, Flores Lujano Janet, Martín Trejo Jorge Alfonso, Mata Rocha Minerva, Medina Sansón Aurora, Espinoza Hernández Laura Eugenia, Peñaloza Gonzalez José Gabriel, Espinosa Elizondo Rosa Martha, Flores Villegas Luz Victoria, Amador Sanchez Raquel, Pérez Saldívar María Luisa, Sepúlveda Robles Omar Alejandro, Rosas Vargas Haydeé, Jiménez Morales Silvia, Galindo Delgado Patricia, Mejía Aranguré Juan Manuel, Alaez Verson Carmen
机构信息
Laboratorio de Diagnóstico Genómico, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE), Mexico City, Mexico.
出版信息
Front Pediatr. 2022 Jul 11;10:899742. doi: 10.3389/fped.2022.899742. eCollection 2022.
BACKGROUND
In Mexico, the incidence of acute myeloid leukemia (AML) has increased in the last few years. Mortality is higher than in developed countries, even though the same chemotherapy protocols are used. CCAAT Enhancer Binding Protein Alpha () mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients.
AIM OF THE STUDY
To identify the mutational landscape of the gene in pediatric patients with AML and assess its influence on clinical features and overall survival (OS).
MATERIALS AND METHODS
DNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of was performed in 80 patients.
RESULTS
was mutated in 12.5% (10/80) of patients. Frameshifts at the N-terminal region were the most common mutations 57.14% (8/14). biallelic ( ) mutations were identified in five patients. M2 subtype was the most common in positive patients ( ) ( = 0.009); 50% of the patients had a WBC count > 100,000 at diagnosis ( = 0.004). OS > 1 year was significantly better in negative ( ) patients ( = 0.0001). patients (either bi- or monoallelic) had a significantly lower OS ( = 0.002). Concurrent mutations in , , and genes were found in individuals. Their contribution to poor OS cannot be ruled out.
CONCLUSION
CEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of was in the range reported for pediatric AML (4.5-15%). mutations showed a negative impact on OS as opposed to the results of other studies.
背景
在墨西哥，急性髓系白血病（AML）的发病率在过去几年有所上升。尽管采用了相同的化疗方案，但其死亡率仍高于发达国家。CCAAT增强子结合蛋白α（CEBPA）突变在AML中较为常见，影响预后，并有助于确定治疗策略。墨西哥儿童AML患者的CEBPA突变谱及其临床意义尚未得到评估。
研究目的
确定儿童AML患者中CEBPA基因的突变情况，并评估其对临床特征和总生存期（OS）的影响。
材料与方法
在诊断时从骨髓穿刺物中提取DNA。对80例患者进行了CEBPA的靶向大规模平行测序。
结果
12.5%（10/80）的患者发生了CEBPA突变。N端区域的移码突变是最常见的突变类型，占57.14%（8/14）。在5例患者中鉴定出双等位基因（biallelic）CEBPA突变。M2亚型在CEBPA阳性患者中最为常见（P = 0.009）；50%的CEBPA阳性患者在诊断时白细胞计数>100,000（P = 0.004）。CEBPA阴性（P = 0.0001）患者的OS>1年明显更好。CEBPA突变患者（双等位基因或单等位基因）的OS明显更低（P = 0.002）。在3例个体中发现了CEBPA、FLT3和NPM1基因的并发突变。不能排除它们对不良OS的影响。
结论
首次评估了墨西哥儿童AML患者的CEBPA突变谱及其临床意义。CEBPA突变频率在儿童AML报道的范围内（4.5 - 15%）。与其他研究结果相反，CEBPA突变对OS有负面影响。
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