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Acute Leukemias

Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases

Leukemia volume 23, pages 85–94 (2009)Cite this article

Abstract

The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy-related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T-myeloid progenitor.

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Acknowledgements

This study was supported by Inserm, Institut Paoli-Calmettes and grants from Association pour la Recherche sur le Cancer (2007; AM).

Author information

Author notes

  1. A Murati, C Gervais and N Carbuccia: These authors contributed equally to this work.

Authors and Affiliations

  1. Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France

    A Murati, N Carbuccia, P Finetti, N Cervera, J Adélaïde, S Olschwang, F Bertucci, M Chaffanet, M-J Mozziconacci & D Birnbaum

  2. Laboratoire d'Hématologie, CHU de Hautepierre, Strasbourg, France

    C Gervais, S Struski & M Lessard

  3. Laboratoire d’Hématologie, Hôpital Cardiologique-Haut Lévêque, Bordeaux, France

    E Lippert

  4. Laboratoire de Cytogénétique, CHU du Bocage, Dijon, France

    F Mugneret

  5. Laboratoire d’Hématologie, CHU Lyon Sud, Lyon, France

    I Tigaud

  6. Département de Génétique, Centre Henri Becquerel, Rouen, France

    D Penther & C Bastard

  7. Centre de Génétique Médicale, Ghent, Belgique

    B Poppe & F Speleman

  8. Laboratoire de Génétique, CHU d’Angers, Angers, France

    L Baranger

  9. Service de Génétique, Hôpital Maison Blanche, Reims, France

    I Luquet & P Cornillet-Lefebvre

  10. Laboratoire d’Hématologie, Hôpital Nord, Saint-Etienne, France

    N Nadal

  11. Laboratoire de Cytogénétique Hématologique, Hôpital Pitié-Salpêtrière, Paris, France

    F Nguyen-Khac

  12. Laboratoire de Cytogénétique Onco-Hématologique, Hôpital Saint-Antoine, Paris, France

    C Pérot

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  1. A Murati
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Correspondence to D Birnbaum.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Murati, A., Gervais, C., Carbuccia, N. et al. Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases. Leukemia 23, 85–94 (2009). https://doi.org/10.1038/leu.2008.257

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