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Acute myeloid leukemia

Polycomb repressive complex 2 haploinsufficiency identifies a high-risk subgroup of pediatric acute myeloid leukemia

Leukemia volume 32, pages 1878–1882 (2018)Cite this article

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Human polycomb proteins exert their epigenetic functions as part of nuclear multimeric complexes, of which Polycomb Repressive Complexes PRC1 and PRC2 are the best characterized [1]. A variety of alterations in Polycomb protein level and function have been described in hematological malignancy. Reports of PRC1 component changes are essentially limited to overexpression, as has been seen in acute myeloid leukemia (AML) and myelodysplastic syndrome [2, 3]. Described PRC2 alterations are more diverse. On the one hand, the occurrence of EZH2 gain-of-function mutations suggests that PRC2 is oncogenic in non-Hodgkin’s lymphoma [4]. In contrast, mutations that cause reduced PRC2 function are commonly found in the early thymic precursor (ETP) subgroup of T-acute lymphoblastic leukemia [5, 6], and have also been reported in myeloid neoplasia [7, 8]. These mutations have not previously been reported to correlate with prognosis, and the biological consequences of altered Polycomb function in most hematological malignancies remain unclear.

In order to characterize the prevalence and clinico-biology of Polycomb gene alterations in pediatric AML, we performed targeted genetic analysis of leukemic DNA extracted from 222 patients treated during the French national ELAM02 study (see Supplementary Files “ELAM02 Key Trial Information” and “ELAM02 Full Protocol French Version”).

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Acknowledgements

The current study was supported by the Institut National du Cancer Projet Caramel (INCA-DGOS_5797). The ELAM02 trial was supported by a grant from the French Ministry of Health (PHRC-K 2003 no 03142) and was sponsored by the Assistance Publique-Hôpitaux de Paris (Département de la Recherche Clinique et du Développement). We would like to thank all patients, families, and staff at participating centers in the trial. JB was supported by a Kay Kendall Leukemia Fund Intermediate Research Fellowship. The Necker laboratory also received funding from the Association Laurette Fugain and La ligue contre le Cancer. The Trousseau laboratory was also supported by the Association Laurette Fugain and La Fondation de France.

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  1. Jonathan Bond

    Present address: School of Medicine and Systems Biology Ireland, University College Dublin, Dublin 4, Ireland

Authors and Affiliations

  1. Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut national de recherche médicale (INSERM) U1151, Paris, France

    Jonathan Bond, Guillaume Hypolite, Vahid Asnafi & Elizabeth Macintyre

  2. Laboratory of Onco-Haematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France

    Jonathan Bond, Guillaume Hypolite, Vahid Asnafi & Elizabeth Macintyre

  3. Medical Genetics Institute, Jeanne de Flandre Hospital, Centre Hospitalier Universitaire (CHU), Lille, France

    Elise Labis

  4. Cancer Research Institute, INSERM Unité Mixte de Recherche (UMR)-S 1172, F-59000, Lille, France

    Elise Labis, Alice Marceau-Renaut, Nicolas Duployez & Claude Preudhomme

  5. CHU Lille, Laboratory of Hematology, F-59000, Lille, France

    Alice Marceau-Renaut, Nicolas Duployez & Claude Preudhomme

  6. Clinical Haematology and Cellular Therapy Department, Hospital Saint-Antoine, APHP, Paris, France

    Myriam Labopin

  7. EBMT ALWP Office, Hôpital Saint-Antoine, APHP, Paris, France

    Myriam Labopin

  8. Universite Pierre et Marie Curie Univ Paris 06, Paris, France

    Myriam Labopin & Hélène Lapillonne

  9. INSERM UMRs 938, CDR Saint-Antoine, F-75012, Paris, France

    Myriam Labopin & Hélène Lapillonne

  10. Department of Pediatric Haematology, University Hospital of La Timone, Marseille, France

    Gérard Michel

  11. Department of Pediatric Hematology and Oncology, Children’s Hospital, Bordeaux, France

    Stéphane Ducassou

  12. Department of Pediatric Haematology and Oncology, Hôpital Armand Trousseau, AP-HP, Paris, France

    Hélène Boutroux, Arnaud Petit & Guy Leverger

  13. Department of Pediatric Hematology-Oncology, Jeanne de Flandre Hospital, CHRU, Lille, France

    Brigitte Nelken

  14. Institute of Pediatric Haematology and Oncology, Hospices Civils de Lyon, Lyon, France

    Yves Bertrand

  15. Department of Pediatric Hematology and Immunology, AP-HP, Robert Debré Hospital, Paris, France

    André Baruchel

  16. Haematology Laboratory, Hôpital Armand Trousseau, AP-HP, Paris, France

    Hélène Lapillonne

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  1. Jonathan Bond
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  18. Hélène Lapillonne
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Correspondence to Jonathan Bond or Hélène Lapillonne.

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The authors declare that they have no conflict of interest.

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Co-first authors: Jonathan Bond and Elise Labis.

Co-directing authors: Jonathan Bond and Hélène Lapillonne.

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Bond, J., Labis, E., Marceau-Renaut, A. et al. Polycomb repressive complex 2 haploinsufficiency identifies a high-risk subgroup of pediatric acute myeloid leukemia. Leukemia 32, 1878–1882 (2018). https://doi.org/10.1038/s41375-018-0187-9

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