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Establishment and characterization of TK-ALCL1: a novel NPM-ALK-positive anaplastic large-cell lymphoma cell line

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Abstract

TK-ALCL1, a novel anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) cell line, was established from the primary tumor site of a 59-year-old Japanese male patient. The immune profile of TK-ALCL1 corresponds to that seen typically in primary ALCL cells, i.e., positive for ALK, CD30, EMA, and CD4, but negative for CD2, CD3, CD5, CD8a, and EBV-related antigens. The rearrangement of the T cell receptor-gamma locus shows that TK-ALCL1 is clonally derived from T-lineage lymphoid cells. FISH and RT-PCR analysis revealed that TK-ALCL1 has the nucleophosmin (NPM)-ALK fusion transcript, which is typical for ALK+ ALCL cell lines. When TK-ALCL1 was subcutaneously inoculated into 6-week-old BALB/c Rag2−/−/Jak3−/− (BRJ) mice, it formed tumor masses within 4–6 weeks. Morphological, immunohistochemical, and molecular genetic investigations confirmed that the xenograft and the original ALCL tumor were identical. The ALK inhibitors Alectinib and Lorlatinib suppressed proliferation in a dose-dependent manner. Thus, TK-ALCL1 provides a useful in vitro and in vivo model for investigation of the biology of ALK+ ALCL and of novel therapeutic approaches targeting ALK.

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The data of this cell line are not applicable.

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Acknowledgements

The authors would like to thank the staff of Tochigi Cancer Center operation room for their support in handling the samples, Ms. Sawako Fujikawa for technical assistance, and Ms. Michiko Teramoto for secretarial assistance.

Funding

This research was funded by Strategic Core Technology Advancement Program (Supporting Industry Program) from Ministry of Economy, Trade and Industry, Japan.

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Authors and Affiliations

  1. Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection & Graduate, School of Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuou-ku, Kumamoto, 860-0811, Japan

    Prin Sungwan, Jutatip Panaampon, Ryusho Kariya & Seiji Okada

  2. Division of Hematologic Neoplasia, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Jutatip Panaampon

  3. Institute of Industrial Nanomaterials, Kumamoto University, 2-39-1 Kurokami, Chuou-ku, Kumamoto, 860-8555, Japan

    Ryusho Kariya & Seiji Okada

  4. Division of Musculoskeletal Oncology and Orthopaedics Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

    Satoshi Kamio, Rumi Nakagawa, Toru Hirozane & Kazutaka Kikuta

  5. Clinical Laboratory Center, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

    Yukiko Ogura

  6. Division of Diagnostic Pathology, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan

    Makoto Abe & Kaoru Hirabayashi

  7. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto, 860-0556, Japan

    Yukio Fujiwara

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  1. Prin Sungwan
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Contributions

Conceptualization, K.K. and S.O.; methodology, P.S., J.P., R.K., and S.O.; software, P.S.; validation, P.S., J.P., Y.F., and S.O.; formal analysis, P.S., Y.S, R.T., T.O., and H.Y.; investigation, P.S., Y.F., S.O.; resources, S.K., R.N., T.H., Y. O., M. A., and K.H.; data curation, R.N.; writing—original draft preparation, P.S. and J.P.; writing—review and editing, K.K. and S.O.; visualization, P.S., Y.O., M.A., K.H., and S.O.; supervision, K.K., K.H., and S.O.; project administration, K.K. and S.O.; funding acquisition, S.O. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Seiji Okada.

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The authors declare that they have no conflict of interest.

Ethical approval and consent to participate

The use of clinical materials for this study was approved by the Institutional Review Board of Tochigi Cancer Center and the Faculty of Life Science Kumamoto University Ethics Committee (30-78-20-2020119). Informed consent was obtained from the donor. Note: TK-ALCL1 is available from corresponding author upon request. The authors are planning to deposit TK-ALCL1 to Japanese Collection of Research Bioresources (JCRB) cell bank (Osaka, Japan).

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Sungwan, P., Panaampon, J., Kariya, R. et al. Establishment and characterization of TK-ALCL1: a novel NPM-ALK-positive anaplastic large-cell lymphoma cell line. Human Cell (2024). https://doi.org/10.1007/s13577-024-01077-8

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