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PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma

Leukemia volume 31, pages 1633–1637 (2017)Cite this article

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The latest revision of the WHO classification recognizes anaplastic lymphoma kinase-negative (ALK-) anaplastic large-cell lymphoma (ALCL), as a distinct type of mature T-cell lymphoma.1 Although ALK- ALCL is genetically heterogeneous, recent studies have shown convergent mutations and kinase fusions that lead to constitutive activation of the JAK/STAT3 pathway.2 ALK- ALCL is clearly different from ALK+ ALCL, a tumor that frequently carries t(2;5)(p23;q35),3 resulting in the NPM-ALK oncogenic kinase, which among other pathways, also activates JAK/STAT3.4

PD-1/PD-L1 immune checkpoint regulation has been under intense investigation in the era of immunotherapy.5 PD-1 blockade has shown very promising clinical responses in patients with classical Hodgkin lymphoma (HL),6 and similar immunotherapy approaches are currently being tested in B- and T-cell non-Hodgkin lymphoma types. The genetic basis of PD-L1 expression has been investigated recently in classical HL and diffuse large B-cell lymphoma (DLBCL).7, 8 In HL, copy gains of the 9p24.1 locus and PD-L1/PD-L2 gene amplification were detected in over 90% of cases and associated with PD-L1 overexpression and shorter progression-free survival.8 By contrast, genetic alterations, including chromosomal gains (12%), amplifications (3%) and translocations (4%) of the PD-L1/PD-L2 locus were reported at a much lower frequency in DLBCL.7 Therefore, it seems that PD-L1/PD-L2 gene amplification is not a common mechanism for PD-L1 expression in aggressive non-Hodgkin lymphomas, unlike classical HL, and other mechanisms underlying PD-L1 expression likely exist.9

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Acknowledgements

GZR is a recipient of a Radiumhemmets Forskningsfonder grant (Sweden). NT is a recipient of a Hellenic Association for Molecular Cancer Research (HAMCR) scholarship.

Author contributions

VA, NT, DC, LK, ED and TP performed research, analyzed the data and contributed to the writing of the paper. LJM, KY and VL contributed vital reagents or clinical samples and also contributed to the writing of the paper. GZR conceived the hypothesis, designed research, analyzed the data and wrote the paper.

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Authors and Affiliations

  1. Department of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden

    V Atsaves, N Tsesmetzis, D Chioureas, L Kis, T Panaretakis, D Grander & G Z Rassidakis

  2. Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden

    L Kis & G Z Rassidakis

  3. Department of Pathology, St Jude Children’s Research Hospital, Memphis, TN, USA

    V Leventaki

  4. Department of Pathology, University of Crete Medical School, Heraklion Crete, Greece

    E Drakos

  5. Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    L J Medeiros, K H Young & G Z Rassidakis

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  1. V Atsaves
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Correspondence to G Z Rassidakis.

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Atsaves, V., Tsesmetzis, N., Chioureas, D. et al. PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia 31, 1633–1637 (2017). https://doi.org/10.1038/leu.2017.103

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