EBV, HCMV, HHV6, and HHV7 screening in bone marrow samples from children with acute lymphoblastic leukemia
A Morales-Sánchez1, E N Pompa-Mera2, A Fajardo-Gutiérrez3
1Unidad de Investigación Médica en Epidemiología Clínica, Hospital de Pediatría, CMN Siglo-XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc 330, Colonia Doctores, 06720 México, DF, Mexico ; Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colonia Doctores, 06720 México, DF, Mexico ; Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, DF, Mexico.
Abstract:
Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.
Insights
This study investigated human herpes viruses in childhood acute lymphoblastic leukemia (ALL) in Mexico. Results indicate these viruses are unlikely to cause ALL or affect patient prognosis.
Area of Science:
- Pediatric Oncology
- Virology
- Epidemiology
Background:
- Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer globally, with high incidence rates in Mexico.
- An infectious etiology for ALL is hypothesized, prompting investigation into potential viral agents.
- Lymphotropic herpes viruses are considered candidates due to their known transforming mechanisms and association with human cancers.
Purpose of the Study:
- To investigate the direct role of Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and human herpesvirus 7 (HHV7) in the development of childhood ALL.
- To determine if these herpes viruses are present in leukemic cells and if they contribute to the initial genetic lesions of ALL.
- To assess the association of these viral infections with the prognosis of childhood ALL in Mexican children.
Main Methods:
- Screening of viral genomes (EBV, HCMV, HHV6, HHV7) in 70 bone marrow samples from children with ALL.
- Utilized standard and nested polymerase chain reaction (PCR) techniques for sensitive viral detection.
- Statistical analysis to evaluate the presence of viruses and their correlation with disease onset and prognosis.
Main Results:
- Viral genomes were detected at low levels, exclusively by the more sensitive nested PCR.
- Viral genomes were not consistently found in all leukemic cells, suggesting they are not involved in initial genetic damage.
- No significant association was found between detected herpes virus infections or coinfections and the prognosis of childhood ALL.
Conclusions:
- The study provides strong evidence against the involvement of EBV, HCMV, HHV6, and HHV7 in the genesis of childhood ALL in the Mexican population.
- Low-level viral detection suggests infection is not a primary factor in the initiation of ALL.
- Herpes virus infections do not appear to influence the clinical outcome or prognosis of childhood ALL.
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