Molecular analysis of the PML/RARα chimeric gene in pediatric acute promyelocytic leukemia

J. R. Kane, D. R. Head, Louisa Balazs, M. C. Hulshof, T. A. Motroni, S. C. Raimondi, A. J. Carroll, F. C. Behm, R. A. Krance, S. A. Shurtleff, J. R. Downing

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Abstract

Acute promyelocytic leukemia (APL) is characterized cytogenetically by the t(15;17)(q22;qll-21) translocation. To compare molecular events among pediatric and adult APL cases, we designed two sets of oligonucleotide primers using published cDNA sequence for PML/RARα fusion transcripts, and undertook reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 22 US pediatric cases of APL. PML/RARα fusion transcripts were detected in all APL cases, including two cases lacking cytogenetic evidence of t(15;17). Breakpoint usage in PML was determined using a combination of PCR amplification with differing 5' primers, junction-specific probes, and sequence analysis in selected cases. Consistent with previously published data, case analysis demonstrated fusion products resulting from three breakpoint cluster regions (bcr) in PML, and a single breakpoint region in intron 2 of RARα. Transcripts resulting from breakpoints in bcr1 were detected in 59% of cases, bcr2 in 27% and bcr3 in 14%. This distribution is dissimilar to that observed in adults, where bcr2 comprises a lesser and bcr3 a greater portion of cases. These results suggest that the pathogenesis of the t(15;17) in APL may differ among patient sets. RT-PCR with these primer sets is a reliable method for detecting PML/RARα chimeric transcript in t(15;17) containing APL.

Original languageEnglish (US)
Pages (from-to)1296-1302
Number of pages7
JournalLeukemia
Volume10
Issue number8
StatePublished - Jan 1 1996

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Acute Promyelocytic Leukemia
Pediatrics
Genes
Reverse Transcriptase Polymerase Chain Reaction
DNA Primers
Cytogenetics
Introns
Sequence Analysis
Complementary DNA
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Kane, J. R., Head, D. R., Balazs, L., Hulshof, M. C., Motroni, T. A., Raimondi, S. C., ... Downing, J. R. (1996). Molecular analysis of the PML/RARα chimeric gene in pediatric acute promyelocytic leukemia. Leukemia, 10(8), 1296-1302.

Molecular analysis of the PML/RARα chimeric gene in pediatric acute promyelocytic leukemia. / Kane, J. R.; Head, D. R.; Balazs, Louisa; Hulshof, M. C.; Motroni, T. A.; Raimondi, S. C.; Carroll, A. J.; Behm, F. C.; Krance, R. A.; Shurtleff, S. A.; Downing, J. R.

In: Leukemia, Vol. 10, No. 8, 01.01.1996, p. 1296-1302.

Research output: Contribution to journalArticle

Kane, JR, Head, DR, Balazs, L, Hulshof, MC, Motroni, TA, Raimondi, SC, Carroll, AJ, Behm, FC, Krance, RA, Shurtleff, SA & Downing, JR 1996, 'Molecular analysis of the PML/RARα chimeric gene in pediatric acute promyelocytic leukemia', Leukemia, vol. 10, no. 8, pp. 1296-1302.
Kane JR, Head DR, Balazs L, Hulshof MC, Motroni TA, Raimondi SC et al. Molecular analysis of the PML/RARα chimeric gene in pediatric acute promyelocytic leukemia. Leukemia. 1996 Jan 1;10(8):1296-1302.
Kane, J. R. ; Head, D. R. ; Balazs, Louisa ; Hulshof, M. C. ; Motroni, T. A. ; Raimondi, S. C. ; Carroll, A. J. ; Behm, F. C. ; Krance, R. A. ; Shurtleff, S. A. ; Downing, J. R. / Molecular analysis of the PML/RARα chimeric gene in pediatric acute promyelocytic leukemia. In: Leukemia. 1996 ; Vol. 10, No. 8. pp. 1296-1302.
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abstract = "Acute promyelocytic leukemia (APL) is characterized cytogenetically by the t(15;17)(q22;qll-21) translocation. To compare molecular events among pediatric and adult APL cases, we designed two sets of oligonucleotide primers using published cDNA sequence for PML/RARα fusion transcripts, and undertook reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of 22 US pediatric cases of APL. PML/RARα fusion transcripts were detected in all APL cases, including two cases lacking cytogenetic evidence of t(15;17). Breakpoint usage in PML was determined using a combination of PCR amplification with differing 5' primers, junction-specific probes, and sequence analysis in selected cases. Consistent with previously published data, case analysis demonstrated fusion products resulting from three breakpoint cluster regions (bcr) in PML, and a single breakpoint region in intron 2 of RARα. Transcripts resulting from breakpoints in bcr1 were detected in 59{\%} of cases, bcr2 in 27{\%} and bcr3 in 14{\%}. This distribution is dissimilar to that observed in adults, where bcr2 comprises a lesser and bcr3 a greater portion of cases. These results suggest that the pathogenesis of the t(15;17) in APL may differ among patient sets. RT-PCR with these primer sets is a reliable method for detecting PML/RARα chimeric transcript in t(15;17) containing APL.",
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