International Journal of Hematology

, Volume 104, Issue 3, pp 330–337 | Cite as

Transition of adult T-cell leukemia/lymphoma clones during clinical progression

  • Sakura Aoki
  • Sanaz Firouzi
  • Yosvany López
  • Tadanori Yamochi
  • Kazumi Nakano
  • Kaoru Uchimaru
  • Atae Utusnomiya
  • Masako Iwanaga
  • Toshiki WatanabeEmail author
Rapid Communication


Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the transformation of HTLV-1-infected T cells. ATLL, especially its aggressive form, is known for its poor prognosis, even with intensive chemotherapy. ATLL cells are considered to be monoclonal; however, multiclonal proliferation or emergence of a new clone over time has been reported based on Southern blot analysis, although direct molecular evidence remains elusive. Furthermore, it is thought that clonal change may be a cause of early drug resistance in ATLL. To directly analyze potential clonal changes in ATLL during its clinical course, we used inverse PCR to detect integration sites in combination with a newly developed method using next-generation sequencing, and compared ATLL cell clonality at different time points. The results of inverse PCR indicated that the major clone was altered in three of 19 patients. Together with results from five patients, using this new method, we found direct evidence of clonal change occurring during the clinical course or in response to chemotherapy in ATLL. These results also highlight the importance of clonality analysis for understanding the mechanisms of ATLL development and drug resistance.


Provirus integration site Clonal change Tag-NGS method 



This work was supported by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest.


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Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Sakura Aoki
    • 1
  • Sanaz Firouzi
    • 1
  • Yosvany López
    • 2
  • Tadanori Yamochi
    • 1
  • Kazumi Nakano
    • 1
  • Kaoru Uchimaru
    • 3
  • Atae Utusnomiya
    • 4
  • Masako Iwanaga
    • 5
  • Toshiki Watanabe
    • 1
    Email author
  1. 1.Department of Computational Biology and Medical Sciences, Graduate School of Frontier SciencesThe University of TokyoTokyoJapan
  2. 2.Laboratory of Functional Analysis in Silico, Human Genome Center, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.Hematology/Oncology, Research Hospital, the Institute of Medical SciencesThe University of TokyoTokyoJapan
  4. 4.Department of HematologyImamura Bun-in HospitalKagoshimaJapan
  5. 5.Department of Frontier Life ScienceNagasaki University Graduate School of Biomedical SciencesNagasakiJapan

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