AI Article Synopsis

  • - Adult T-cell leukemia/lymphoma (ATL) is found in about 5% of individuals infected with the human T-lymphotropic virus type 1 (HTLV-1), and it's traditionally seen as a monoclonal disease where a single T-cell clone becomes dominant and cancerous.
  • - A study analyzed 197 ATL cases to examine the genetic features of the virus within these cancerous cells compared to nonmalignant cells, revealing that 91% of dominant clones had only one provirus and indicating that just being oligoclonal does not lead to cancer.
  • - Gene analysis linked ATL to genetic integration near host genes associated with blood cancers, and across all HTLV-1 cases, there

Article Abstract

Adult T-cell leukemia/lymphoma (ATL) occurs in ∼5% of human T-lymphotropic virus type 1 (HTLV-1)-infected individuals and is conventionally thought to be a monoclonal disease in which a single HTLV-1(+) T-cell clone progressively outcompetes others and undergoes malignant transformation. Here, using a sensitive high-throughput method, we quantified clonality in 197 ATL cases, identified genomic characteristics of the proviral integration sites in malignant and nonmalignant clones, and investigated the proviral features (genomic structure and 5' long terminal repeat methylation) that determine its capacity to express the HTLV-1 oncoprotein Tax. Of the dominant, presumed malignant clones, 91% contained a single provirus. The genomic characteristics of the integration sites in the ATL clones resembled those of the frequent low-abundance clones (present in both ATL cases and carriers) and not those of the intermediate-abundance clones observed in 24% of ATL cases, suggesting that oligoclonal proliferation per se does not cause malignant transformation. Gene ontology analysis revealed an association in 6% of cases between ATL and integration near host genes in 3 functional categories, including genes previously implicated in hematologic malignancies. In all cases of HTLV-1 infection, regardless of ATL, there was evidence of preferential survival of the provirus in vivo in acrocentric chromosomes (13, 14, 15, 21, and 22).

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064332PMC
http://dx.doi.org/10.1182/blood-2014-02-553602DOI Listing

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