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Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias

Leukemia volume 24, pages 469–473 (2010)Cite this article

The majority of adult acute myeloid leukemias (AMLs) have normal cytogenetics and lack a balanced translocation with a known fusion gene. They occur de novo or after a chronic phase (hereafter called primary and secondary, respectively). They are poorly understood and heterogeneous in terms of bioclinical presentation and prognosis, as well as in terms of molecular targets. The identification of mutations in several genes, such as NPM1 and FLT3, has revealed prognosis subgroups and modified their clinical management.1 A better molecular characterization should further improve both the understanding of the physiopathology and the treatment of these leukemias.

The additional sex comb-like 1 (ASXL1) gene, located in the chromosomal region 20q11, belongs to a family of three identified members that encode poorly characterized proteins regulating chromatin remodeling. The ASXL proteins contain a C-terminal PHD (Plant Homeo Domain) finger and belong to the polycomb and trithorax complexes, which regulate the genetic program of stem cells. We have recently shown that ASXL1 is mutated in roughly 10% of myelodysplastic syndromes,2 10% of myeloproliferative neoplasms3 and 40% of chronic myelomonocytic leukemias.2 Using array comparative genomic hybridization (aCGH), we also observed a deletion of the ASXL1 locus in a myelodysplastic syndrome case.2 These observations suggest that ASXL1 is a tumor suppressor whose haploinsufficiency has a role in myeloid diseases. The predicted truncated ASXL1 protein would lack its PHD finger, which could prevent it from binding methylated histone lysines and interacting with chromatin modifiers, thus enhancing self-renewal in hematopoietic progenitors.4

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Acknowledgements

This work was supported by the Inserm, Institut Paoli-Calmettes and grants from the Association pour la Recherche contre le Cancer (AM, no. 4929) and Fondation de France (DB, Comité Leucémie).

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Author notes

  1. N Carbuccia and V Trouplin: These authors contributed equally to this work.

  2. Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France

Authors and Affiliations

  1. Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 Inserm, Institut Paoli-Calmettes, Marseille, France

    N Carbuccia, V Trouplin, V Gelsi-Boyer, A Murati, J Rocquain, J Adélaïde, S Olschwang, M Chaffanet, D Birnbaum & M J Mozziconacci

  2. Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France

    V Gelsi-Boyer, A Murati, S Olschwang, L Xerri, N Vey & M J Mozziconacci

  3. Faculté de Médecine, Université de la Méditerrané, Marseille, France

    V Gelsi-Boyer, L Xerri & N Vey

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Correspondence to M J Mozziconacci.

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Carbuccia, N., Trouplin, V., Gelsi-Boyer, V. et al. Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia 24, 469–473 (2010). https://doi.org/10.1038/leu.2009.218

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