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Identification of MYC mutations in acute myeloid leukemias with NUP98–NSD1 translocations

Leukemia volume 30, pages 1621–1624 (2016)Cite this article

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The NUP98 gene, located on chromosomal band 11p15, is recurrently translocated with at least 28 fusion partners in hematological malignancies.1 One of the most frequent NUP98 rearrangements in acute myeloid leukemias (AML) results in the cryptic NUP98– NSD1 translocation. NUP98– NSD1 leukemias typically have a normal karyotype and develop in younger (<20 years) patients who show high white blood cell (WBC) counts at diagnosis. The NUP98–NSD1 fusion transcript encodes for a protein that includes the glycine–leucine–phenylalanine–glycine repeat motifs of NUP98 fused to the PHD and SET domains of NSD1.

Microarray studies have revealed that NUP98– NSD1 AML show a gene expression profile2 characterized by high expression levels of HOXA and HOXB genes. Targeted mutation analyses of this disease have identified a very high frequency of FLT3 internal tandem duplications (ITDs) and, to a lesser degree, recurrent mutations in genes such as WT1, NRAS and KRAS.2, 3, 4 Using an approach based on next-generation transcriptome sequencing and group-by-group comparison recently developed for EVI1 and MLL-rearranged AML,5, 6 we herein report the transcriptome and mutational landscape of NUP98–NSD1 AML.

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Acknowledgements

This work was supported by the Government of Canada through Genome Canada and the Ministère de l’économie, de l’innovation et des exportations du Québec through Génome Québec, with supplementary funds from AmorChem. We thank Muriel Draoui for project coordination and Sophie Corneau for sample coordination, as well as Marianne Arteau and Raphaëlle Lambert at the IRIC genomics platform for RNA sequencing. The dedicated work of BCLQ staff, namely, Giovanni d’Angelo, Claude Rondeau and Sylvie Lavallée, is also acknowledged. GS and JH are recipients of research chairs from the Canada Research Chair program and Industrielle-Alliance (Université de Montréal). BCLQ is supported by grants from the Cancer Research Network of the Fonds de recherche du Québec–Santé. RNA-Seq read mapping and transcript quantification were performed on the supercomputer Briaree from the Université de Montréal, managed by Calcul Québec and Compute Canada. The operation of this supercomputer is funded by the Canada Foundation for Innovation (CFI), NanoQuébec, RMGA and the Fonds de recherche du Québec – Nature et technologies (FRQ-NT). V-PL is supported by a postdoctoral fellowship jointly supported by Hôpital Maisonneuve-Rosemont’s Foundation and by Cole Foundation. Accession codes: GSE49642, GSE52656, GSE62190, GSE66917, GSE67039.

Author contributions

V-PL analyzed the exomes and transcriptomes of all samples, generated the corresponding figures, tables and Supplementary Material, and co-wrote the paper. GS contributed to project conception and coordination, and co-wrote the paper. JH contributed to project conception, analyzed the cytogenetic and FISH studies, provided all the AML samples and edited the manuscript. PG processed the raw NGS data. GB co-developed the analytical pipeline. SL was responsible for supervision of the bioinformatics team and of statistical analyses. IB performed data validation. SG performed immunoblot experiment.

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Authors and Affiliations

  1. The Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada

    V-P Lavallée, S Lemieux, G Boucher, P Gendron, I Boivin, S Girard, J Hébert & G Sauvageau

  2. Division of Hematology, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada

    V-P Lavallée, J Hébert & G Sauvageau

  3. Department of Computer Science and Operations Research, Université de Montréal, Montréal, Québec, Canada

    S Lemieux

  4. Quebec Leukemia Cell Bank, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada

    J Hébert & G Sauvageau

  5. Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada

    J Hébert & G Sauvageau

Authors
  1. V-P Lavallée
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  2. S Lemieux
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  3. G Boucher
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  4. P Gendron
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  5. I Boivin
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  6. S Girard
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  7. J Hébert
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  8. G Sauvageau
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Corresponding authors

Correspondence to J Hébert or G Sauvageau.

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Lavallée, VP., Lemieux, S., Boucher, G. et al. Identification of MYC mutations in acute myeloid leukemias with NUP98–NSD1 translocations. Leukemia 30, 1621–1624 (2016). https://doi.org/10.1038/leu.2016.19

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