title: Viral infection-oxidative stress/DNA damage-aberrant DNA methylation: separate or interrelated events responsible for genetic instability and childhood ALL development?
abstract: Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates in a single B- or T-lymphocyte progenitor and is characterized by a range of numeric and structural chromosomal aberrations. Although, so far no clear cause can be found for ALL the most commonly recognized and strongest causal factor is infection. However, an interesting question is how viral infection may be responsible for genetic changes that lead to lymphoid cell transformation. A plausible mechanism by which infection might impact the process of leukemogenesis via genetic alteration is through: oxidative stress/DNA damage which is closely linked with inflammation, aberrant expression of AID/ABOBEC family enzymes which may be responsible for massive mutation introduction and alteration of DNA methylation, leading to changes in the expression of hematopoietic genes. In this review we propose several specific molecular mechanisms which link infection with all the above-mentioned processes. The most likely event which links common virus infection with ALL pathogenesis is aberrant expression of AID/APOBEC. This event may be directly responsible for the introduction of point mutations (as the result of cytosine or 5-methylcytosine deamination and formation of G:U or G:T misspairs) as well as changes in DNA methylation status.
authors.affiliation: Department of Clinical Biochemistry, Nicolaus Copernicus University in Torun, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland. Electronic address: ryszardo@cm.umk.pl.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Olinski
authors.affiliation: Department of Paediatrics, Haematology and Oncology, Nicolaus Copernicus University in Torun, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
authors.affiliation: District Health Center in Kartuzy, Poland.
authors.forename: Elwira
authors.initials: E
authors.lastname: Olinska
authors.affiliation: Department of Clinical Biochemistry, Nicolaus Copernicus University in Torun, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gackowski
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D019175:DNA Methylation; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D042822:Genomic Instability / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D014777:Virus Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism*
keywords: 5-Methylcytosine; Acute lymphoblastic leukemia; Deaminases; Epigenetics; Oxidative stress; Viral infection