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Chronic lymphocytic leukemia

Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors

Leukemia volume 33, pages 1801–1805 (2019)Cite this article

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Chronic lymphocytic leukemia (CLL) displays remarkable clinical heterogeneity, likely attributed to the underlying biological diversity [1]. This claim is supported by the fact that certain immunogenetic and/or genomic features identify subgroups of CLL patients with distinct prognosis and outcome [2,3,4]. Indeed, determination of the somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) genes expressed by the clonotypic B cell receptor (BcR) and screening for aberrations οf the TP53 gene are nowadays considered essential for clinical decision making [5]. A cautionary note appears warranted when utilizing biomarkers, where the prognosis is usually assessed assuming stable predictability over the disease course; this hypothesis, however, is often unrealistic as it concerns genomic aberrations [6, 7]. Therefore, arguably, the prognostic power of a given biomarker may, instead, heavily depend on the time distance from diagnosis.

To address this issue we investigated in early-stage CLL patients the impact over-time of SHM within the IGHV genes, i.e., the segregation into mutated (M-CLL) and unmutated CLL (U-CLL), on the evolution of risk for CLL progression and need of treatment. Our analysis was based on hazard curves instead of Kaplan–Meier survival curves, which represent, respectively, the “instant” risk for the event at each time-point instead of the cumulative risk [8, 9].

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Acknowledgements

This project has received funding from the European Union’s Horizon 2020 (EU H2020) research and innovation programme under the Marie Sklodowska-Curie grant agreement No 702714 CLLassify; the EU H2020 project AEGLE; the EU H2020 project MEDGENET; the Swedish Cancer Society, the Swedish Research Council, Knut and Alice Wallenberg Foundation, Karolinska Institutet, Stockholm, the Lion’s Cancer Research Foundation, Uppsala, the Marcus Borgström Foundation and Selander’s Foundation, Uppsala; CEITEC MEYS CR project LQ1601; EC is supported by grants from Instituto de Salud Carlos III (PMP15/00007, CIBERONC and ERA-NET TRANSCAN initiative (TRS-2015-00000143) AC15/00028.

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Authors and Affiliations

  1. Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece

    Theodoros Moysiadis & Kostas Stamatopoulos

  2. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Panagiotis Baliakas, Richard Rosenquist & Kostas Stamatopoulos

  3. Division of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    Davide Rossi

  4. Department of Hemato-Oncology, Belfast City Hospital, Belfast, UK

    Mark Catherwood

  5. Cancer Genomics, Academic Unit of Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton, Southampton, UK

    Jonathan C. Strefford

  6. Hematology Department, Hospital Clinic, Barcelona, Spain

    Julio Delgado

  7. Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece

    Achilles Anagnostopoulos & Niki Stavroyianni

  8. Hematology Department, Nikea General Hospital, Pireaus, Greece

    Chrysoula Belessi

  9. Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic

    Sarka Pospisilova

  10. Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK

    David Oscier

  11. Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    Gianluca Gaidano

  12. Hematopathology Section, Laboratory of Pathology, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain

    Elias Campo

  13. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Richard Rosenquist

  14. Division of experimental Oncology, IRCCS Istituto Scientfico San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy

    Paolo Ghia

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  1. Theodoros Moysiadis
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  2. Panagiotis Baliakas
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  14. Richard Rosenquist
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Correspondence to Kostas Stamatopoulos.

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Conflict of interest

KS and PG received research support from Janssen Pharmaceuticals, Gilead Sciences, Novartis SA, Abbvie and Roche Hellas. The remaining authors declare that they have no conflict of interest.

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Moysiadis, T., Baliakas, P., Rossi, D. et al. Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors. Leukemia 33, 1801–1805 (2019). https://doi.org/10.1038/s41375-018-0322-7

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