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NUP98–HMGB3: a novel oncogenic fusion

Leukemia volume 24, pages 654–658 (2010)Cite this article

NUP98 is a promiscuous gene involved in chromosomal aberrations with more than 20 different partner genes in a variety of human hematological malignancies.1, 2 These rearrangements all lead to the expression of hybrid proteins that start with the amino-terminal moiety of NUP98. This amino-terminal domain contains multiple copies of a glycine-leucine-phenylalanine-glycine core motif, known to recruit the CBP/p300 acetyltransferases.3 Evidence from overexpressions studies in mouse bone marrow (BM) progenitors indicates that the NUP98-fusion proteins induce leukemic transformation through the upregulation of Hoxa genes and the Hox cofactor Meis1. Expression of Hoxa, most frequently Hoxa7, Hoxa9 and Hoxa10 is postulated to induce a self-renewal stem cell-like program that likely contributes to the leukemic process.4, 5

High mobility group (HMG) proteins are non-histone chromatin-associated proteins that bind to DNA with limited or no sequence specificity. Among them, HMGB proteins are important architectural facilitators of nucleosome remodelling and possibly of transcription factor's interaction with DNA (for a review, see Travers6). The expression of the murine Hmgb3 gene is tightly regulated during hematopoiesis and is required in early steps of hematopoietic stem cell development in which it regulates cell-fate decisions. It is expressed in common myeloid and lymphoid progenitors (CMP and CLP) and except in the erythroid cells, it must be downregulated for the proper differentiation of both lineages to take place.7, 8 Hmgb3 RNA has recently been found to be part of an embryonic stem cell-like transcription signature that was defined in mouse models of mixed-lineage leukemia (MLL)-mediated leukemic transformation and was also reported to be transiently upregulated during myeloid differentiation.9

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Acknowledgements

We thank Julie Bergeron for help in analyses of PB and BM smears. AP acknowledges the support from the Fondation pour la Recherche Medicale (FRM; Paris, France) and Association pour la recherche sur le Cancer (ARC; Villejuif, France). This work was funded by grants from ARC and Institut National du Cancer (INCa).

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  1. A Petit

    Present address: 5Present address: AP-HP, Hôpital Armand Trousseau, Service d’Hématologie et d’Oncologie Pédiatrique, 26 avenue du Docteur Arnold Netter, Paris, F-75012, France,

  2. C Schluth

    Present address: 6Present address: Service de cytogénétique, Centre de biologie et de pathologie Est, Hospices civils de Lyon, 59 boulevard Pinel, Bron, F-69677, France,

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (Inserm), Hôpital Necker-Enfants malades, 149 rue de Sèvres, Paris, F-75015, France

    A Petit, C Ragu, V Della-Valle, G Soler, C Schluth, I Radford, C Ottolenghi, O A Bernard, V Penard-Lacronique & S P Romana

  2. Université Paris Descartes, 12 rue de l'Ecole de Médecine, Paris, F-75006, France

    A Petit, C Ragu, V Della-Valle, G Soler, C Schluth, I Radford, C Ottolenghi, O A Bernard, V Penard-Lacronique & S P Romana

  3. Laboratoire de Cytogénétique Onco-Hématologique-Hôpital Timone Enfants, 264 rue Saint-Pierre, Marseille, F-13385, France

    M J Mozziconacci & M Lafage-Pochitaloff

  4. Laboratoire de Cytogénétique, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris, F-75015, France

    G Soler, I Radford & S P Romana

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Correspondence to V Penard-Lacronique or S P Romana.

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Petit, A., Ragu, C., Della-Valle, V. et al. NUP98–HMGB3: a novel oncogenic fusion. Leukemia 24, 654–658 (2010). https://doi.org/10.1038/leu.2009.241

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