Castañeda-Partida Laura, Ocadiz-Delgado Rodolfo, Sánchez-López José Manuel, García-Villa Enrique, Peñaloza-González José Gabriel, Velázquez-Aviña Martha Margarita, Torres-Nava José Refugio, Martín-Trejo Jorge Alfonso, Solís-Labastida Karina, Guerra-Castillo Francisco Xavier, Bekker-Méndez Vilma Carolina, Rosales-García Víctor Hugo, Romero-Rodríguez Dámaris, Mojica-Espinoza Raúl, Mendez-Tenorio Alfonso, Ramírez-Calzada Crystel A, Álvarez-Ríos Elízabeth, Mejía-Aranguré Juan Manuel, Gariglio Patricio
Laboratorio de Genética Toxicológica, Biología. Facultad de Estudios Profesionales Iztacala (FESI), Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, Estado de México, Mexico.
Laboratorio de Oncología Molecular, Departamento de Genética y Biología Molecular. Centro de Investigación y de Estudios Avanzados (Cinvestav), Ciudad de México, Mexico.
Discov Oncol. 2022 Apr 21;13(1):28. doi: 10.1007/s12672-022-00480-7.
Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.
墨西哥城是全球急性淋巴细胞白血病（ALL）发病率最高的地区之一，患者生存率低，复发率高。为了更深入了解墨西哥儿童B-ALL的分子特征，我们使用荧光激活细胞分选方案，从4例B-ALL患者的骨髓和9例外周血样本中分离出CD10 + / CD19 +前体B淋巴母细胞。整体基因表达谱（骨髓与外周血）显示136个差异表达基因；62个上调（45.6%），74个下调（54.4%）。计算皮尔逊相关系数以确定前B淋巴母细胞群体之间的相似性。我们选择了26个高度显著的基因，并通过RT-qPCR验证了21个（CNN3、STON2、CALN1、RUNX2、GADD45A、CDC45、CDC20、PLK1、AIDA、HCK、LY86、GPR65、PIK3CG、LILRB2、IL7R、TCL1A、DOCK1、HIST1H3G、PTPN14、CD72和NT5E）。对总表达矩阵的基因集富集分析以及对136个差异表达基因的 Ingenuity 通路分析表明，骨髓中的细胞周期发生了改变，有4个过表达基因（PLK1、CDC20、CDC45和GADD45A），以及参与B细胞分化的IL7R和PIK3CG低表达。对通过TARGET计划收集的15例西班牙裔B-ALL患者的骨髓和10例外周血样本进行的比较生物信息学分析，证实了观察到的基因，但PIK3CG除外。我们得出结论，所研究的墨西哥和西班牙裔B-ALL患者存在共同的驱动改变和组织学类型特异性突变，这可能有助于风险分层和诊断准确性，并作为潜在的治疗靶点。
