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Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large cell lymphoma

Leukemia volume 32, pages 565–569 (2018)Cite this article

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Anaplastic large cell lymphomas (ALCLs) constitute a group of peripheral (that is, post-thymic) T-cell non-Hodgkin’s lymphomas (PTCLs) with overlapping pathologic characteristics, but varying clinical and molecular features. Specifically, ALCLs share cytological and immunophenotypic features, including consistent expression of the lymphocyte activation marker, CD30.1 The World Health Organization (WHO) classifies ALCLs by their clinical presentation (systemic or cutaneous) and whether or not they bear rearrangements of the anaplastic lymphoma kinase gene, ALK (ALK-positive ALCL and ALK-negative ALCL, respectively).2

ALK-positive ALCL is characterized by a unique gene expression signature that distinguishes it from ALK-negative ALCL.3, 4, 5 ALK rearrangements have a broad spectrum of functional consequences, prominent among which is activation of the signal transduction protein STAT3 (signal transducer and activator of transcription 3).6 Analogously, STAT3 may be activated in ALK-negative ALCLs by somatic events involving non-ALK tyrosine kinase genes, including rearrangements of the TYK2 or ROS1 tyrosine kinase genes as well as mutations in JAK1 or STAT3 itself.7, 8 However, the full spectrum of tyrosine kinases involved in ALK-negative ALCL pathogenesis and growth remains incompletely understood, as does the similarity of these events to the molecular signature identified in ALK-positive ALCLs. For example, a subclass of ALK-negative ALCLs expressing aberrant transcripts of the ERBB4 tyrosine kinase gene had a gene expression signature distinct from ALK-positive ALCLs.9

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Acknowledgements

This study was supported by Award Numbers R01 CA177734 (to ALF), P30 CA15083 (Mayo Clinic Cancer Center) and P50 CA97274 (University of Iowa/Mayo Clinic Lymphoma SPORE) from the National Cancer Institute; CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Science (NCATS); Award Number CI-48-09 from the Damon Runyon Cancer Research Foundation (to ALF); Department of Laboratory Medicine and Pathology and Center for Individualized Medicine, Mayo Clinic; and the Predolin Foundation.

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Author notes

  1. G Hu and S Dasari: These two authors contributed equally to this work.

  2. R L Boddicker and A L Feldman: These two authors contributed equally to this work and serve as co-corresponding authors.

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    G Hu, P T Greipp, H K Benson, J Jen, R L Boddicker & A L Feldman

  2. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    S Dasari, Y Li & J R Cerhan

  3. Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA

    Y W Asmann

  4. Medical Genome Facility, Mayo Clinic, Rochester, MN, USA

    P T Greipp, R A Knudson & B W Eckloff

  5. Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    B K Link

  6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA

    L Jiang

  7. Department of Pathology and Laboratory Medicine, United Health Services Hospitals, Johnson City/Binghamton, NY, USA

    J S Sidhu

  8. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    L E Wellik, T E Witzig & N N Bennani

Authors
  1. G Hu
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Corresponding authors

Correspondence to R L Boddicker or A L Feldman.

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The authors declare no conflict of interest.

Additional information

Author contributions

GH contributed to study design and conducted experiments. SD contributed to study design and analyzed data. HKB, JJ, BWE and LEW conducted experiments. YWA and YL analyzed data. PTG and RAK conducted cytogenetic studies. BKL, JRC, TEW, NNB, JSS and LJ contributed clinical specimens. RLB and ALF designed the study, analyzed data and wrote the manuscript.

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Hu, G., Dasari, S., Asmann, Y. et al. Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large cell lymphoma. Leukemia 32, 565–569 (2018). https://doi.org/10.1038/leu.2017.309

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