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CYTOGENETICS AND MOLECULAR GENETICS

The 5th edition of the WHO classification of haematolymphoid tumors: comments from the Groupe Francophone de Cytogénétique Hématologique (GFCH)

Leukemia volume 37, pages 946–947 (2023)Cite this article

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We read with great interest the recent publications on the Fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) [1, 2]. We congratulate all the co-authors on the new edition, which reflects the most up-to-date knowledge on this topic. Based on its collective expertise, the Groupe Francophone de Cytogénétique Hématologique (GFCH) would like to share some comments on items that require clarification.

Chromosomal abnormalities (CAs, including translocations and inversions) have been removed from the WHO-HAEM5 classification of most of the haematological malignancies with defining genetic abnormalities caused by this type of defect - especially acute leukaemia. In B-cell lymphoblastic leukaemia/lymphoma (B-ALL), for example, the t(9;22)(q34.1;q11.2) no longer appears, and only the BCR::ABL1 fusion is mentioned. Acute myeloid leukaemia (AML) with t(8;21)(q22;q22.1) is now only designated by RUNX1::RUNX1T1. The main argument put forward by the authors for removing the CA designations from these specific entities is “to allow for the application of differing techniques for their detection”. The GFCH is fully aware that molecular technologies have become essential for the diagnostic work-up of these diseases. Nonetheless, in routine practice, chromosome banding analysis (CBA) cannot yet be fully replaced by high-throughput analyses. CBA is still clinically relevant for the genetic characterization of acute leukaemia. A very small subset of relevant, recurrent CAs escapes detection with CBA due to cryptic rearrangements (translocations or insertions) or culture failures. Despite these well-known and minor limitations, CBA currently remains the most widespread technique and is available in many laboratories – including those located in low-income countries. Importantly, CBA provides (i) an overview of the tumour genome, (ii) the ability to identify many recurrent CAs, and (iii) single-cell resolution and thus insights into clonal evolution. Cytogenetics also provides valuable mechanistic information. The spatial proximity of chromatin loci and the high frequencies of contact between translocation partner genes (i.e. BCR and ABL1, or IGH and MYC) have been demonstrated in normal hematopoietic nuclei – thus predisposing these loci to chromosomal translocation [3, 4]. In our view, it is essential not to erase fundamental knowledge that is useful for understanding haematological diseases. This knowledge also reflects the major, current contribution of CBA to diagnostic and therapeutic decision-making in the management of patients with haematological cancer. Hence, we believe that it is important to maintain both components of each recurrent CA within specific acute leukaemia entities.

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Authors and Affiliations

  1. Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, INSERM UMRS, 1138, Paris, France

    Florence Nguyen-Khac

  2. Sorbonne Université, Paris, France

    Florence Nguyen-Khac

  3. Service d’Hématologie Biologique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France

    Florence Nguyen-Khac

  4. CHU Bordeaux, Laboratoire d’Hématologie Biologique, F-33000, Bordeaux, France

    Audrey Bidet

  5. Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France

    Marie-Bérengère Troadec

  6. CHRU Brest, Service de génétique, Unité de génétique chromosomique, Brest, France

    Marie-Bérengère Troadec

  7. Service de Cytogénétique Médicale, CHU Estaing, 1 place Lucie et Raymond Aubrac, 63003, Clermont-Ferrand, France

    Lauren Veronese

  8. Gustave Roussy, Génétique des tumeurs, 144 rue Edouard Vaillant, 94805, Villejuif, France

    Nathalie Auger

  9. Institut de Génétique Médicale - Hôpital Jeanne de Flandre - CHRU de Lille, Av. Eugène Avinée, 59037, Lille Cedex, France

    Agnes Daudignon

  10. Service de génétique chromosomique et moléculaire - C.H.U. Dijon - Plateau Technique de Biologie, 2 rue Angélique Ducoudray, 21070, Dijon Cedex, France

    Nathalie Nadal

  11. Laboratoire de Génétique Oncologique, Centre Henri Becquerel, rue d’Amiens, 76038, Rouen, France

    Dominique Penther

  12. Center for Human Genetics, University Hospitals Leuven, and KU Leuven, Leuven, Belgium

    Lucienne Michaux

  13. Laboratoire de Cytogénétique Hématologique CHU Timone Aix Marseille University, Marseille, France

    Marina Lafage-Pochitaloff

  14. Laboratoire de Génétique des Hémopathies - CHU GRENOBLE, 38043, Grenoble Cedex 09, France

    Christine Lefebvre

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  1. Florence Nguyen-Khac
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Contributions

FN-K conceived and supervised the manuscript. CL, FN-K, AB, and ML-P wrote the section’s writing. M-BT, LV, LM contributed to writing the manuscript. FN-K, AB, M-BT, LV, NA, AD, NN, DP, LM, ML-P and CL reviewed the full manuscript.

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Correspondence to Florence Nguyen-Khac.

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Nguyen-Khac, F., Bidet, A., Troadec, MB. et al. The 5th edition of the WHO classification of haematolymphoid tumors: comments from the Groupe Francophone de Cytogénétique Hématologique (GFCH). Leukemia 37, 946–947 (2023). https://doi.org/10.1038/s41375-023-01821-3

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