Spliceosome mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia

Virginie Chesnais, Olivier Kosmider, Frederik Damm, Raphael Itzykson, Olivier A Bernard, Eric Solary and Michaela Fontenay _

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Oncotarget. 2012; 3:1284-1293. https://doi.org/10.18632/oncotarget.749

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Virginie Chesnais1,2,3,4, Olivier Kosmider1,2,3,4,5, Frederik Damm6,7, Raphael Itzykson6,8,9, Olivier A. Bernard6,7, Eric Solary6,8,9, Michaela Fontenay1,2,3,4,5

1 Institut Cochin,

2 INSERM U1016,

3 CNRS UMR8104;

4 Université Paris Descartes, Paris France;

5 Assistance Publique-Hôpitaux de Paris, Service d’Hématologie Biologique, Hôpitaux universitaires Paris-Centre, Paris, France;

6 Institut Gustave Roussy, Villejuif, France;

7 INSERM, U985, Villejuif, France;

8 INSERM U1009, Villejuif, France ;

9 Université Paris Sud-11, Faculté de Médecine, Le Kremlin-Bicêtre, France.


Michaela Fontenay, email:

Keywords: splicing, alternative splicing, mutations, myeloid malignancies

Received: November 13, 2012, Accepted: November 30, 2012, Published: November 30, 2012


The recently discovered spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies. A substantial proportion of patients with myelodysplastic syndromes (MDS), chronic myelomonocytoic leukemia (CMML) or chronic lymphocytic leukemia (CLL) harbor such mutations, which are often missense in type. Genotype-phenotype correlations have been observed, including the clustering of ring sideroblasts with SF3B1 mutations in MDS. Spliceosome mutations might result in defective small nuclear ribonucleoprotein complexes assembly on the pre-mRNA, deregulated global and alternative mRNA splicing, nuclear-cytoplasm export, and unpliced mRNA degradation, and thus may alter the expression of multiple genes. In the current review, we discuss the potential role of these mutations in cell transformation and how they could impact the therapeutic approaches.

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