Lösemi ve Hodgkin Lenfomalı Pediatrik Hastalarda Epstein-Barr Virüsü Genomunun Tespiti: Türkiye'de Pediatrik Kanserlerde Viral Etiyoloji

Abstract

Amaç: Kanser, yaygın görülmesi ve zorlu tedavi süreci ile karakterize yaygın bir hastalıktır. Virüsler de dahil olmak üzere birçok etken hem yetişkinlerde hem de çocuklarda kanserin potansiyel nedenleri olarak tanımlanmış olsa da kanserlerin patogenezi tam olarak aydınlatılamamıştır. Bu çalışma, B hücreli akut lenfoblastik lösemi (ALL), T hücreli ALL, Hodgkin lenfoma tanısı almış ve lösemi ile lenfoma nükseden pediatrik hastalardan elde edilen kan örneklerinde (n=64), insan T-hücreli lenfotropik virüs tip 1 (HTLV-1), Epstein-Barr virüsü (EBV), Kaposi sarkom ilişkili herpesvirüs (KSHV) ve insan parvovirus B19'un (HPV B19) varlığını incelemeyi amaçlamıştır. Gereç ve Yöntemler: Hastalardan hem tedavi öncesi hem tedavi sonrası dönemlerinde tam kan örnekleri alınmış ve bu örneklerde HTLV-1, EBV, KSHV ve HPV B19 viral genom varlığını tespit etmek için polimeraz zincir reaksiyonu (PCR) ve gerçek zamanlı PCR yapılmıştır. Pozitif örneklerden Sanger sekanslama ile sekans analizi yapılmış ve filogenetik analizler gerçekleştirilmiştir. Bulgular: Toplam 64 örnek analiz edildiğinde, HTLV-1, KSHV ve HPV B19'un negatif olduğu belirlenmiştir. Ancak, EBV genomu ALL ve Hodgkin lenfoma hastalarından altı örnekte (%9.37) tespit edilmiştir; bu örnekler hem tedavi öncesi (n=3) hem de tedavi sonrası (n=3) vakalarda saptanmıştır. Pozitif EBV örneklerinin sekanslama sonrasında ve GenBank'ta bulunan diğer EBV dizileri ile hizalanması, birbirleri ile yüksek derecede benzerlik gösterdiğini ortaya koymuştur. Sonuç: Bulgularımız, EBV'nin, lösemi ve Hodgkin lenfomalı pediatrik kanser vakalarında etkili olan viral ajanlardan biri olabileceğini düşündürmektedir. Bu nedenle, Türkiye'deki bu hasta popülasyonunda EBV genomunun varlığını test edilmesi önemli olabilecektir. Bu veri, pediatrik kanserlerin temelindeki viral etiyolojiyi daha iyi anlamamıza ve gelecekte hedefe yönelik tanı ve tedavi stratejilerinin geliştirilmesine yardımcı olacaktır.

Keywords

• İnsan T-hücreli lenfotropik virüs tip 1
• Epstein-Barr virüsü
• Kaposi sarkom ilişkili herpesvirus
• insan parvovirus B19
• akut lenfoblastik lösemi
• Hodgkin lenfoma

Supporting Institution

Kırıkkale Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

2016/116

DETECTION OF EPSTEIN-BARR VIRUS GENOME IN PEDIATRIC PATIENTS WITH LEUKEMIA AND HODGKIN LYMPHOMA: VIRAL ETIOLOGY IN PEDIATRIC CANCERS IN TÜRKİYE

Abstract

Objective: Cancer is a pervasive disease characterized by its widespread occurrence and challenging treatment process. While numerous agents, including viruses, have been identified as potential causes of cancer in both adults and children, the complete pathogenesis of cancers remains incompletely elucidated. This study aimed to examine the presence of four viral agents, namely Human T-cell Lymphotropic Virus Type 1 (HTLV-1), Epstein-Barr Virus (EBV), Kaposi's Sarcoma- Associated Herpesvirus (KSHV), and Human Parvovirus B19 (HPV B19), in blood samples obtained from pediatric patients (n=64) diagnosed with B cell acute lymphoblastic leukemia (ALL), T cell ALL, Hodgkin lymphoma, and patients with relapsed leukemia and lymphoma. Material and Methods: The whole blood samples collected from the patients during the pre-treatment and post-treatment periods underwent polymerase chain reaction (PCR) and real- time PCR to identify the presence of the viral genomes of HTLV-1, EBV, KSHV, and HPV B19. The samples that tested positive were subsequently subjected to Sanger sequencing, followed by phylogenetic analysis. Results: Among a total of 64 samples analyzed, HTLV-1, KSHV, and HPV B19 were found to be negative. However, EBV genome was detected in six samples (9.37%) from patients with ALL and Hodgkin lymphoma, comprising both pre- treatment (n=3) and post-treatment (n=3) cases. Subsequent sequencing and alignment of the positive EBV samples with other EBV sequences deposited in GenBank revealed a high degree of similarity. Conclusion: Our findings suggest that EBV may be one of the viral agents implicated in pediatric cancer cases involving leukemia and Hodgkin lymphoma. Therefore, it is recommended to consider testing for the presence of EBV genome in these patient populations within the context of Türkiye. This information contributes to a better understanding of the viral etiology underlying pediatric cancers, enabling the development of targeted diagnostic and therapeutic strategies in the future.

Keywords

• Human T-cell lymphotropic virus type 1
• Epstein-Barr virus
• Kaposi
• human parvovirus B19
• acute lymphoblastic leukemia
• Hodgkin lymphoma

Supporting Institution

Scientific Research Projects Coordination Unit of Kırıkkale University

Project Number

2016/116

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