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Acute myeloid leukemia

Granulomonocytic progenitors are key target cells of azacytidine in higher risk myelodysplastic syndromes and acute myeloid leukemia

Leukemia volume 32, pages 1856–1860 (2018)Cite this article

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The hypomethylating agent (HMA) azacytidine (AZA) is approved in higher risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Identifying HMA biomarkers is difficult, possibly owing to uncertainties regarding the target cell populations of HMA.

Granulomonocytic progenitors (GMP, Lin-CD34+/CD38+/CD123+/CD45RA+) and lymphoid-primed multipotential progenitors (LMPP, Lin-/CD34+/CD38−/CD90−/CD45RA+) have leukemia initiating capacity (LIC) in AML [1]. Serial flow cytometry assessment in MDS/AML patients treated with AZA suggested that these compartments may be targeted by HMAs [2, 3]. Several groups have investigated the clonal dynamics of total bone marrow cells in MDS/AML patients treated with HMA, often finding an erosion of mutational burden in responding patients [4,5,6,7]. We conducted a pilot study to assess the clonal architecture of GMP and LMPP at initial response evaluation in MDS/AML patients treated with AZA (Supplementary Figure 1 and Supplementary Methods).

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Fig. 1
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Acknowledgements

This project has been supported by Saint Louis Institute (SLI, ‘Institut Hospitalo-Universitaire’, Agence Nationale pour la Recherche) and Laurette Fugain Association. We thank the Core Facility of Institut Universitaire d’Hématologie (IUH) and notably Sophie Duchez and Christèle Dolliger for assistance with flow cytometry, and Antonio Alberdi and Julien Pelé for NGS. R.I. is recipient of a Gilead International Research Scholarship in Haematology/Oncology. A.P. is a recipient of the ATIP-AVENIR and the ERC Starting research programs. We acknowledge funding from the National Health and Medical Research Council of Australia (JEP) and the Anthony Rothe Memorial Trust (AU).

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Authors and Affiliations

  1. INSERM/CNRS UMR 944/7212, Paris, France

    Ashfaq Ali, Justine Penneroux, Reinaldo Dal Bello Jr, Aline Massé, Samuel Quentin, Lucie Hernandez, Raouf Ben Abdelali, Jean Soulier, Pierre Fenaux, Emmanuelle Clappier, Lionel Adès, Alexandre Puissant & Raphael Itzykson

  2. Institut Universitaire d’Hématologie, Paris Cancer Research Institute (PACRI), Université Paris Diderot, Paris, France

    Ashfaq Ali, Justine Penneroux, Reinaldo Dal Bello Jr, Aline Massé, Samuel Quentin, Lucie Hernandez, Raouf Ben Abdelali, Hervé Dombret, Jean Soulier, Pierre Fenaux, Emmanuelle Clappier, Lionel Adès, Alexandre Puissant & Raphael Itzykson

  3. Hematology Department, Hopital Saint Louis, Assistance Publique – Hopitaux de Paris, University Paris Diderot, Paris, France

    Reinaldo Dal Bello Jr, Emmanuel Raffoux, Hervé Dombret, Pierre Fenaux, Lionel Adès & Raphael Itzykson

  4. Hematology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Reinaldo Dal Bello Jr

  5. Laboratory of Hematology, Hopital Saint Louis, Assistance Publique – Hopitaux de Paris, University Paris Diderot, Paris, France

    Samuel Quentin, Lucie Hernandez, Raouf Ben Abdelali, Jean Soulier & Emmanuelle Clappier

  6. Lowy Cancer Research Centre, Prince of Wales Clinical School, UNSW Sydney, Sydney, NSW 2025, Australia

    Ashwin Unnikrishnan & John Pimanda

  7. Hematology Laboratory, Biology and Pathology Center, CHRU of Lille, Lille, France

    Aline Renneville & Claude Preudhomme

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  1. Ashfaq Ali
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Correspondence to Raphael Itzykson.

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Conflicts of interest

A.R. and J.P. have received research funding from Celgene. P.F. has received research funding from Celgene, Astex and Janssen. R.I. has received research funding from Janssen.

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Ali, A., Penneroux, J., Dal Bello, R. et al. Granulomonocytic progenitors are key target cells of azacytidine in higher risk myelodysplastic syndromes and acute myeloid leukemia. Leukemia 32, 1856–1860 (2018). https://doi.org/10.1038/s41375-018-0076-2

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