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Genomic and molecular switching in relapsed acute promyelocytic leukemia

Leukemia volume 22, pages 1469–1472 (2008)Cite this article

Acute promyelocytic leukemia (APL) is characterized by a recurrent translocation between chromosomes 15 and 17, resulting in the fusion of the promyelocytic leukemia gene (PML) to the retinoic acid receptor α gene (RARα).1 Among APL cases with a PML-RARα rearrangement, chromosome 15 breakpoints fall within three breakpoint cluster regions (bcrs): bcr1 and bcr3 correspond to PML introns 6 and 3, respectively, whereas bcr2 is located within PML exon 6, or very occasionally within PML exon 5. On the contrary, a single RARα breakpoint region occurs within intron 2.2

A bcr1 breakpoint is reported in approximately 55% of patients and results in an mRNA fusion of PML exon 6 to RARα exon 3, conventionally referred to as the long (L) isoform. A bcr3 breakpoint occurs in approximately 40% of cases and results in an mRNA fusion of PML exon 3 to RARα exon 3, referred to as the short (S) isoform. A bcr2 breakpoint occurs in approximately 5% of patients and usually results in a tripartite mRNA fusion in which part of PML exon 6 is fused to an insert sequence and then to RARα exon 3, where the insert is usually between 3 and 127 base pairs long and has been presumed to be derived from RARα intron 2. Some cases have no inserted nucleotides and instead use a cryptic splice site within PML exon 6 to splice part of this exon in frame to RARα exon 3. Collectively, these transcripts are referred to as the variable (V) isoform.2, 3

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Acknowledgements

The authors thank Ms MVC Pragnell, BA, for language revision of the manuscript. The financial support of Associazione Italiana contro le Leucemie (AIL)-BARI is gratefully acknowledged.

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Authors and Affiliations

  1. Hematology, University of Bari, Bari, Italy

    F Albano, A Pannunzio, L Anelli, A Zagaria, V Liso & G Specchia

  2. DI.GE.MI., University of Bari, Bari, Italy

    M Rocchi

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  1. F Albano
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Correspondence to F Albano.

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Albano, F., Pannunzio, A., Anelli, L. et al. Genomic and molecular switching in relapsed acute promyelocytic leukemia. Leukemia 22, 1469–1472 (2008). https://doi.org/10.1038/sj.leu.2405103

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