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Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies

Leukemia volume 26, pages 2027–2031 (2012)Cite this article

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Abstract

Spliceosome mutations represent a new generation of acquired genetic alterations that affect both myeloid and lymphoid malignancies. A substantial proportion of patients with myelodysplastic syndromes (MDSs) or chronic lymphocytic leukemia (CLL) harbor such mutations, which are often missense in type. Genotype–phenotype associations have been demonstrated for one of these mutations, SF3B1, with ring sideroblasts in MDS and 11q22 deletions in CLL. Spliceosome mutations might result in defective spliceosome assembly, deregulated global mRNA splicing, nuclear-cytoplasm export and altered expression of multiple genes. Such mutations are infrequent in other lymphomas, which instead display a separate group of novel mutations involving genes whose products are believed to affect histone acetylation and methylation and chromatin structure (for example, EZH2 and MLL2). On the other hand, some mutations (for example, NOTCH1) occur in both CLL and other immature and mature lymphoid malignancies. In the current review, we discuss potential mechanisms of cell transformation associated with spliceosome mutations, touch upon the increasing evidence regarding the clonal involvement of hematopoietic stem cells in some cases of otherwise mature lymphoid disorders and summarize recent information on recently described mutations in lymphomas.

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Acknowledgements

Work in the authors’ laboratories was supported by the INSERM, Direction de la recherche clinique AP-HP (PHRC MDS-04), INCa, association Laurette Fugain and labellisation from Ligue Nationale Contre le Cancer. Frederik Damm is supported by a grant from the Deutsche Krebshilfe. We want to thank William Vainchenker, Daniel Birnbaum and Christian Bastard for their helpful discussion.

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Authors and Affiliations

  1. Institut Gustave Roussy, Villejuif, France

    F Damm & O A Bernard

  2. INSERM, U985, Villejuif, France

    F Damm & O A Bernard

  3. Université Paris Sud-11, Orsay, France

    F Damm & O A Bernard

  4. Service d’Hématologie Biologique, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    F Nguyen-Khac

  5. INSERM U872,

    F Nguyen-Khac

  6. Université Pierre et Marie Curie-Paris 6, Paris, France

    F Nguyen-Khac

  7. Assistance Publique-Hôpitaux de Paris, Service d’Hématologie Biologique, Hôpital Broca-Cochin-Hôtel-Dieu, Paris, France

    M Fontenay & O A Bernard

  8. Département d’Immunologie et Hématologie, Institut Cochin, Paris, France

    M Fontenay

  9. INSERM U1016, CNRS UMR8104, Paris, France

    M Fontenay

  10. Université Paris Descartes, Paris, France

    M Fontenay

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Damm, F., Nguyen-Khac, F., Fontenay, M. et al. Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies. Leukemia 26, 2027–2031 (2012). https://doi.org/10.1038/leu.2012.86

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