Atypical mRNA Fusions in PML-RARA Positive, RARA-PML Negative Acute Promyelocytic Leukemia

作者：Walz Christoph; Grimwade David; Saussele Susanne; Lengfelder Eva; Haferlach Claudia; Schnittger Susanne; Lafage Pochitaloff Marina; Hochhaus Andreas; Cross Nicholas C P; Reiter Andreas^*

来源：Genes, Chromosomes and Cancer, 2010, 49(5): 471-479.

DOI：10.1002/gcc.20757

Reciprocal RARA-PML transcripts are not detected in similar to 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 HERCI-PML and NT_00974.17-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).

• 出版日期2010-5