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Molecular Medicine

, Volume 17, Issue 11–12, pp 1338–1348 | Cite as

Torque Teno Virus 10 Isolated by Genome Amplification Techniques from a Patient with Concomitant Chronic Lymphocytic Leukemia and Polycythemia Vera

  • Charles C. Chu
  • Lu Zhang
  • Arjun Dhayalan
  • Briana M. Agagnina
  • Amanda R. Magli
  • Gia Fraher
  • Sebastien Didier
  • Linda P. Johnson
  • William J. Kennedy
  • Rajendra N. Damle
  • Xiao-Jie Yan
  • Piers E. M. Patten
  • Saul Teichberg
  • Prasad Koduru
  • Jonathan E. Kolitz
  • Steven L. Allen
  • Kanti R. Rai
  • Nicholas Chiorazzi
Research Article

Abstract

An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility. Using genome amplification methods, we identified a new isolate (BIS8-17) of torque teno virus (TTV) 10. The presence of blood isolate sequence 8–17 (BIS8-17) in the original plasma was confirmed by polymerase chain reaction (PCR), validating the approach, since TTV is a known plasma virus. Subsequent PCR testing of plasmas from additional patients showed that BIS8-17 had a similar incidence (~20%) in CLL (n = 48) or PV (n = 10) compared with healthy controls (n = 52). CLL cells do not harbor BIS8-17; PCR did not detect it in CLL peripheral blood genomic deoxyribonucleic acid (DNA) (n = 20). CLL patient clinical outcome or prognostic markers (immunoglobulin heavy chain variable region [IGHV] mutation, CD38 or zeta-chain associated protein kinase 70kDa [ZAP-70]) did not correlate with BIS8-17 infection. Although not causative to our knowledge, this is the first reported isolation and detection of TTV in either CLL or PV. TTV could serve as a covirus with another infectious agent or TTV variant with rearranged genetic components that contribute to disease pathogenesis. These results prove that this method identifies infectious agents and provides an experimental methodology to test correlation with disease.

Notes

Acknowledgments

We thank Craig Gawel and Dorothy Guzowski (Molecular Biology Core, FIMR) for help with oligonucleotides and sequences; Erin Boyle (FIMR) for sample collection; Angela Tse Chuang Chu for support and encouragement; and Bettie Steinberg, Rosa Catera, Patricia Mongini and Sophia Yancopoulos for scientific discussions. This work was supported in part by a R01 grant from the National Institutes of Health (NIH) (CA81554), a M01 General Clinical Research Center grant from NIH (RR018535), the Ruth E. Raskin Fund of the Jewish Community Foundation, the Karches Foundation, the Prince Family Foundation, the Marks Foundation, the Jerome Levy Foundation, the Leon Levy Foundation and the Joseph Eletto Leukemia Research Fund.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Charles C. Chu
    • 1
    • 2
    • 4
  • Lu Zhang
    • 1
  • Arjun Dhayalan
    • 1
  • Briana M. Agagnina
    • 1
  • Amanda R. Magli
    • 1
  • Gia Fraher
    • 1
  • Sebastien Didier
    • 1
  • Linda P. Johnson
    • 1
  • William J. Kennedy
    • 1
  • Rajendra N. Damle
    • 1
    • 4
  • Xiao-Jie Yan
    • 1
  • Piers E. M. Patten
    • 1
  • Saul Teichberg
    • 3
  • Prasad Koduru
    • 3
    • 6
  • Jonathan E. Kolitz
    • 1
    • 2
    • 4
  • Steven L. Allen
    • 1
    • 2
    • 4
  • Kanti R. Rai
    • 1
    • 7
    • 4
  • Nicholas Chiorazzi
    • 1
    • 2
    • 4
    • 5
  1. 1.The Feinstein Institute for Medical ResearchNorth Shore-Long Island Jewish (LIJ) Health SystemManhassetUSA
  2. 2.Department of MedicineNorth Shore University Hospital, North Shore-LIJ Health SystemManhassetUSA
  3. 3.Department of PathologyNorth Shore University Hospital, North Shore-LIJ Health SystemManhassetUSA
  4. 4.Department of MedicineHofstra North Shore-LIJ School of MedicineHempsteadUSA
  5. 5.Department of Molecular MedicineHofstra North Shore-LIJ School of MedicineHempsteadUSA
  6. 6.Department of PathologyNew York University School of MedicineNew YorkUSA
  7. 7.Department of MedicineLong Island Jewish Medical Center, North Shore-LIJ Health SystemNew Hyde ParkUSA

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