Variant ALK-fusion positive anaplastic large cell lymphoma (ALCL): A population-based paediatric study of the NHL-BFM study group

Jette Luedersen; Udo Zur Stadt; Julia Richter; Ilske Oschlies; Wolfram Klapper; Andreas Rosenwald; Marketa Kalinova; Ingrid Simonitsch-Klupp; Reiner Siebert; Martin Zimmermann; Minyue Qi; Jacqueline Nakel; Katrin Scheinemann; Fabian Knörr; Andishe Attarbaschi; Edita Kabickova; Wilhelm Woessmann; Christine Damm-Welk

doi:10.1111/bjh.19308

Variant ALK-fusion positive anaplastic large cell lymphoma (ALCL): A population-based paediatric study of the NHL-BFM study group

Br J Haematol. 2024 Jan 26. doi: 10.1111/bjh.19308. Online ahead of print.

Authors

Jette Luedersen¹, Udo Zur Stadt², Julia Richter³, Ilske Oschlies³, Wolfram Klapper³, Andreas Rosenwald⁴, Marketa Kalinova^{5

6}, Ingrid Simonitsch-Klupp⁷, Reiner Siebert⁸, Martin Zimmermann⁹, Minyue Qi¹⁰, Jacqueline Nakel¹¹, Katrin Scheinemann^{12

13

14}, Fabian Knörr^{1

15}, Andishe Attarbaschi^{16

17}, Edita Kabickova¹⁸, Wilhelm Woessmann¹, Christine Damm-Welk¹

Affiliations

¹ Paediatric Haematology and Oncology and NHL-BFM Study Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
² Paediatric Haematology and Oncology and CoALL Study Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
³ Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Kiel, Germany.
⁴ Department of Pathology, University of Wuerzburg, Wuerzburg, Germany.
⁵ Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University Prague and University Hospital in Motol, Prague, Czech Republic.
⁶ Department of Pathology, 3rd Faculty of Medicine, Charles University Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
⁷ Department of Pathology, Medical University of Vienna, Vienna, Austria.
⁸ Institute of Human Genetics, Ulm University & Ulm University Medical Centre, Ulm, Germany.
⁹ Department of Paediatric Haematology and Oncology, Hannover Medical School, and NHL-BFM Study Centre, Hannover, Germany.
¹⁰ Bioinformatics Core, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Leibniz Institute of Virology (LIV), Hamburg, Germany.
¹² Division of Paediatric Haematology/Oncology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
¹³ Faculty of Health Science and Medicine, University of Lucerne, Lucerne, Switzerland.
¹⁴ Department of Paediatrics, McMaster Children's Hospital and McMaster University, Hamilton, Ontario, Canada.
¹⁵ Mildred Scheel Cancer Career Centre HaTriCS4, University Medical Centre Hamburg- Eppendorf, Hamburg, Germany.
¹⁶ Department of Paediatric Haematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
¹⁷ St. Anna Children's Cancer Research Institute, Vienna, Austria.
¹⁸ Department of Pediatric Hematology and Oncology, Charles University Prague and University Hospital Motol, Prague, Czech Republic.

PMID: 38279625
DOI: 10.1111/bjh.19308

Abstract

Frequency, distribution and prognostic meaning of ALK-partner genes other than NPM1 in ALK-positive anaplastic large-cell lymphoma (ALCL) are unknown. Forty-nine of 316 ALCL diagnosed in the NHL-BFM study group showed no nuclear ALK expression suggestive of a variant ALK-partner; 41 were analysed by genomic capture high-throughput sequencing or specific RT-PCRs. NPM1::ALK was detected in 13 cases. Among the 28 patients with a non-NPM1::ALK-fusion partner, ATIC (n = 8; 29%) and TPM3 (n = 9; 32%) were the most common. Five of eight patients with ATIC::ALK-positive ALCL relapsed, none of nine with TPM3::ALK. Variant ALK-partners are rare and potentially associated with different prognoses.

Keywords: ALK positive ALCL; non-Hodgkin's lymphoma; variant ALK.

Abstract

Grants and funding