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

Prin Sungwan; Jutatip Panaampon; Ryusho Kariya; Satoshi Kamio; Rumi Nakagawa; Toru Hirozane; Yukiko Ogura; Makoto Abe; Kaoru Hirabayashi; Yukio Fujiwara; Kazutaka Kikuta; Seiji Okada

doi:10.1007/s13577-024-01077-8

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

Hum Cell. 2024 May 16. doi: 10.1007/s13577-024-01077-8. Online ahead of print.

Authors

Prin Sungwan¹, Jutatip Panaampon^{1

2}, Ryusho Kariya^{1

3}, Satoshi Kamio⁴, Rumi Nakagawa⁴, Toru Hirozane⁴, Yukiko Ogura⁵, Makoto Abe⁶, Kaoru Hirabayashi⁶, Yukio Fujiwara⁷, Kazutaka Kikuta⁴, Seiji Okada^{8

9}

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.
² Division of Hematologic Neoplasia, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.
³ Institute of Industrial Nanomaterials, Kumamoto University, 2-39-1 Kurokami, Chuou-ku, Kumamoto, 860-8555, Japan.
⁴ Division of Musculoskeletal Oncology and Orthopaedics Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan.
⁵ Clinical Laboratory Center, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan.
⁶ Division of Diagnostic Pathology, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan.
⁷ Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto, 860-0556, Japan.
⁸ 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. okadas@kumamoto-u.ac.jp.
⁹ Institute of Industrial Nanomaterials, Kumamoto University, 2-39-1 Kurokami, Chuou-ku, Kumamoto, 860-8555, Japan. okadas@kumamoto-u.ac.jp.

PMID: 38755432
DOI: 10.1007/s13577-024-01077-8

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.

Keywords: Anaplastic large-cell lymphoma (ALCL); Anaplastic lymphoma kinase (ALK); Chromosomal translocation; Human cell line; Nucleophosmin (NPM); Tyrosine kinase receptor.