Atypical mRNA fusions in <i>PML‐RARA</i> positive, <i>RARA‐PML</i> negative acute promyelocytic leukemia

Genes Chromosomes and Cancer - Tập 49 Số 5 - Trang 471-479 - 2010
Christoph Walz1,2, David Grimwade3, Susanne Saußele1, Eva Lengfelder1, Claudia Haferlach4, Susanne Schnittger4, Marina Lafage‐Pochitaloff5, Andreas Hochhaus6,1, Nicholas C.P. Cross7, Andreas Reiter1
1III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany
2Pathologisches Institut, Universitätsmedizin Mannheim, Mannheim, Germany
3Department of Medical and Molecular Genetics, King’s College London School of Medicine, London, UK
4Münchner Leukämie-Labor, München, Germany
5Department of Genetics, CHU Timone, AP-HM and Université de la Méditerranée, Marseille, France
6Department Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany
7Wessex Regional Genetics Laboratory, Salisbury and Human Genetics Division, University of Southampton, Salisbury, UK

Tóm tắt

AbstractReciprocal RARA‐PML transcripts are not detected in ∼25% of patients with PML‐RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML‐RARA positive/RARA‐PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT‐PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML‐CDC6‐RARA forward DNA fusion and expressed a chimeric PML‐CDC6‐RARA mRNA in addition to a PML‐RARA. The other two had HERC1‐PML and NT_009714.17‐PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA‐PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA‐PML fusion transcripts, which were not identified by conventional RT‐PCR assays. This study demonstrates that the frequency of RARA‐PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12). © 2010 Wiley‐Liss, Inc.

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Genes Chromosomes and Cancer

Tập 49 Số 5

471-479

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