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The presence of a single PML-RARA isoform lacking exon 5 in FISH-negative APL samples

Leukemia volume 22, pages 200–203 (2008)Cite this article

Acute promyelocytic leukemia (APL) represents about 10% of acute myeloid leukemias and is characterized by a specific translocation between chromosomes 15 and 17, resulting in the fusion of the putative transcription factor promyelocytic leukemia gene (PML) to the retinoic acid receptor α gene (RARA).1 This fusion PML-RARA protein blocks differentiation at the promyelocytic stage and is uniquely sensitive to all-trans retinoic acid and arsenic trioxide with significantly improved outcome of APL patients. However, complete remission is not always durable and relapse is often associated with resistance.2

Breakpoints in the PML gene in APL are grouped in three cluster regions (bcr1–3) with fusion to a single breakpoint region in the RARA gene. The common breakpoints in APL are bcr1, referring to breakpoint within PML intron 6 and bcr3, with breakpoint in PML intron 3. As the PML gene consists of nine exons, from which exons 4–6 may be skipped, in the bcr1-type APL several spliced transcripts are generated.2, 3 It was suggested that the different PML splice variants could add new functional domains to the protein.2 In APL, similar splicing occurs in the PML portion within the PML-RARA fusion molecule. Several sets of primers have been defined that allow the amplification of PML-RARA transcripts. Using a nested reverse transcriptase-PCR (RT-PCR) approach, the different isoforms are amplified, generating several transcripts, among which is an isoform lacking PML exon 5. The PML protein consists of an N-terminal proline-rich motif, a cysteine-rich motif, an α-helical domain, a leucine zipper homologous region and a serine-rich motif.2 The absence of exon 5, part of the α-helical domain, was suggested to result in all-trans retinoic acid resistance.4

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Author notes

  1. O Ashur-Fabian and L Trakhtenbrot: These authors contributed equally to this work.

  2. E-mail: Osnat.Ashur@sheba.health.gov.il

Authors and Affiliations

  1. Cancer Research Centre and Lily and Edmond Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel

    O Ashur-Fabian, L Trakhtenbrot, D Dominissini, M Koren-Michowitz, G Rechavi & N Amariglio

  2. Division of Hematology, Sheba Medical Center, Tel-Hashomer, Israel

    O Ashur-Fabian, L Trakhtenbrot, M Koren-Michowitz, A Nagler & N Amariglio

  3. Sackler Medical School, Tel Aviv University, Tel Aviv

    O Ashur-Fabian, L Trakhtenbrot, D Dominissini, M Koren-Michowitz, A Nagler, G Rechavi & N Amariglio

  4. Bone Marrow Transplantation, Sheba Medical Center, Tel-Hashomer, Israel

    A Nagler

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  1. O Ashur-Fabian
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Please note that the author names listed in the Advance Online Publication (AOP) version of this article were listed incorrectly. These have now been corrected in this print version.

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Ashur-Fabian, O., Trakhtenbrot, L., Dominissini, D. et al. The presence of a single PML-RARA isoform lacking exon 5 in FISH-negative APL samples. Leukemia 22, 200–203 (2008). https://doi.org/10.1038/sj.leu.2404991

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