Occurrence of distinct PML-RAR-α fusion gene isoforms in patients with acute promyelocytic leukemia detected by reverse transcriptase/polymerase chain reaction

S. J. Chen, Z. Chen, A. Chen, J. H. Tong, S. Dong, Z. Y. Wang, S. Waxman, A. Zelent

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

A specific 'nested' reverse transcriptase/polymerase chain reaction (RT/PCR) procedure was used to characterize the expression patterns of PML-RAR-α chimeric mRNAs in 32 patients with acute promyelocytic leukemia (APL). The sensitivity of the technique was such that the fusion gene transcript could be detected from as little as 2.5 μg of total leukemic cell RNA against a background of 1 μg of cellular RNA lacking the PML-RAR-α fusion gene transcript(s). In 19 cases the PML-RAR-α isoform referred to here as long was identified. A short isoform, which in comparison with the long form lacks three PML exons, was detected in 11 other cases. A third PML-RAR-α mRNA isoform, in which the most 3' PML exon present in the long-type isoform was truncated in its sequences lying immediately upstream of RAR-α B region, was found and characterized in a single patient. In one APL patient with a variant translocation t(11;17), the PCR product corresponding to PML-RAR-α chimeric mRNAs could not be amplified despite the presence of RAR-α gene rearrangement. Genomic and PCR analysis showed that the different PML-RAR-α isoforms found in APL patients arise as a result of distinct translocation breakpoints. In each case the exons encoding the B-F regions of RAR-α are expressed and are spliced downstream from variable PML gene exons. The 'nested' RT/PCR analysis of the PML-RAR-α fusion gene proved to be a rapid and sensitive tool for the diagnosis of the APL and for monitoring the residual APL chimeric mRNA expression during complete remission.

Original languageEnglish (US)
Pages (from-to)1223-1232
Number of pages10
JournalOncogene
Volume7
Issue number6
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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