Palma-Lara Icela, Sánchez-Aldana Ana Elena, Jiménez-Hernández Elva, Martínez-Villegas Octavio, Núñez-Enríquez Juan Carlos, Mejía-Aranguré Juan Manuel, Ochoa Sara A, Xicohtencatl-Cortes Juan, Cruz-Córdova Ariadnna, Zavala-Vega Sergio, García-Jiménez Mariana, Contreras-Ramos Alejandra, Torres-Nava José Refugio, Mora-Ramiro Guillermo, Arellano-Galindo José
Molecular and Cellular Morphology Laboratory, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico.
Departamento de Hematología Pediátrica, Centro Médico Nacional la Raza, Instituto Mexicano del Seguro Social, Ciudad de Mexico 02990, Mexico.
Microorganisms. 2020 Jun 26;8(6):958. doi: 10.3390/microorganisms8060958.
NOTCH1 and PAX5 participate in the proliferation and differentiation of B and T lymphocytes. Their expression can be modified by activation of NOTCH1, induced by the Epstein-Barr (EBV) viral proteins identified as LMP1 and LMP2. To identify whether PAX5, NOTCH1, and EBV latency genes participate in the oncogenic process of pediatric patients with classical Hodgkin lymphoma (cHL), the present study aimed to identify the variable expression of NOTCH1 among disease subtypes and to assess its effect on PAX5 expression. A total of 41 paraffin-embedded tissues from Mexican pediatric patients with cHL were analyzed. The expression of CD30, CD20, NOTCH1, PAX5, and LMP1 was evaluated by immunohistochemistry and immunofluorescence. EBV detection was performed by in situ hybridization. Out of all cases, 78% (32/41) of the cHL cases were EBV positive. NOTCH1 expression was detected in 78.1% (25/32) of EBV-positive cases, nodular sclerosis being the most frequent subtype (11/25, 44%). In cases where the expression of both genes was identified, double immunofluorescence assays were conducted, finding no colocalization. We found that Reed-Sternberg cells had aberrant expression compared to their cells of origin (B lymphocytes) due to the molecular mechanisms involved in the loss of expression of PAX5 and that the identification of NOTCH1 could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in pediatric cHL.
NOTCH1和PAX5参与B淋巴细胞和T淋巴细胞的增殖与分化。它们的表达可通过激活NOTCH1来改变，NOTCH1的激活由被鉴定为LMP1和LMP2的爱泼斯坦-巴尔病毒（EBV）蛋白诱导。为了确定PAX5、NOTCH1和EBV潜伏基因是否参与经典型霍奇金淋巴瘤（cHL）儿科患者的致癌过程，本研究旨在确定疾病亚型中NOTCH1的可变表达，并评估其对PAX5表达的影响。对来自墨西哥cHL儿科患者的41份石蜡包埋组织进行了分析。通过免疫组织化学和免疫荧光评估CD30、CD20、NOTCH1、PAX5和LMP1的表达。通过原位杂交进行EBV检测。在所有病例中，78%（32/41）的cHL病例为EBV阳性。在78.1%（25/32）的EBV阳性病例中检测到NOTCH1表达，结节硬化型是最常见的亚型（11/25，44%）。在鉴定出两种基因表达的病例中，进行了双重免疫荧光检测，未发现共定位。我们发现，由于参与PAX5表达缺失的分子机制，里德-斯腾伯格细胞与其起源细胞（B淋巴细胞）相比存在异常表达，并且NOTCH1的鉴定可被视为儿科cHL的候选诊断/预后标志物和治疗靶点。
