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Acute myeloid leukemia

Genetic analysis of therapy-related myeloid neoplasms occurring after intensive treatment for acute promyelocytic leukemia

Leukemia volume 32, pages 2066–2069 (2018)Cite this article

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Therapy-related myeloid neoplasms (t-MN) are severe long-term consequences of cytotoxic therapies, associated with a dismal prognosis. These disorders have been recognized by the World Health Organization classification as a specific subset of myeloid neoplasms, comprising acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients who were exposed to cytotoxic or radiation therapy for an unrelated malignancy or auto-immune disease [1]. Historically, t-MN have been considered as a consequence of DNA damage and oncogenic abnormalities directly induced by cytotoxic therapy in normal hematopoietic stem and progenitor cells [2]. Recent advances in DNA sequencing technologies have considerably improved our understanding of t-MN pathogenesis and provided new insights into t-MN biology. One of the major novel findings that emerged from next-generation sequencing (NGS) studies was that chemotherapy also promotes clonal selection of pre-existing mutant hematopoietic stem cells. This mechanism has been highlighted by Wong et al. for TP53 mutations [3], most of them being loss-of-function mutations that are associated with resistance to chemotherapy.

Acute promyelocytic leukemia (APL) represent 5–10% of all AML, and are characterized by a chromosomal rearrangement involving the retinoic acid receptor alpha (RARA). With the incorporation of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) into the treatment paradigm of APL, this disease has become the most curable subtype of adult AML [4]. However, 1 to 2% of APL treated with ATRA and intensive chemotherapy subsequently develop a t-MN (different from APL), a serious late side effect of this treatment.

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Acknowledgements

The centers of the French Swiss Belgian APL group who entered their patients in APL 2006 trial are to be acknowledged.

Author contributions:

AR, PA, XT, CB, SH, HF, VE, AMR, BC, JF, CT, ED, SP, JL, SC, LA, CP performed research or collected data; AR and PA analyzed data; AR and PF wrote the paper; PF supervised the project. All authors approved the final manuscript.

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Authors and Affiliations

  1. Hematology Laboratory, Biology and Pathology Center, Lille, France

    Aline Renneville, Alice Marceau-Renaut & Claude Preudhomme

  2. Service d’Hématologie Seniors, Saint-Louis Hospital, AP-HP, Paris, France

    Philippe Attias, Cécile Bally, Lionel Adès & Pierre Fenaux

  3. Hematology Department, Lyon Sud Hospital, Pierre Bénite, France

    Xavier Thomas

  4. Hematology Laboratory, Lyon Sud Hospital, Pierre Bénite, France

    Sandrine Hayette

  5. Hematology Department, André Mignot Hospital, Le Chesnay, France

    Hassan Farhat

  6. Hematology Laboratory, Avicenne Hospital, AP-HP, Bobigny, France

    Virginie Eclache

  7. Service de Biologie Cellulaire, Saint-Louis Hospital, AP-HP, Paris, France

    Bruno Cassinat

  8. Hematology Laboratory, CHU Limoges, Limoges, France

    Jean Feuillard

  9. Hematology Laboratory, Andre Mignot Hospital, Le Chesnay, France

    Christine Terré

  10. Institut Universitaire de Cancérologie de Toulouse, CHU de Toulouse, Toulouse, France

    Eric Delabesse

  11. Hematology Department, CHU Grenoble Alpes, Grenoble, France

    Sophie Park

  12. Biostatistic Department, Saint-Louis Hospital, AP-HP, Paris, France

    Julie Lejeune & Sylvie Chevret

  13. Groupe Français des myélodysplasies (GFM), Paris, France

    Pierre Fenaux

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  1. Aline Renneville
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Correspondence to Pierre Fenaux.

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The authors declare that they have no conflict of interest.

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Renneville, A., Attias, P., Thomas, X. et al. Genetic analysis of therapy-related myeloid neoplasms occurring after intensive treatment for acute promyelocytic leukemia. Leukemia 32, 2066–2069 (2018). https://doi.org/10.1038/s41375-018-0137-6

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