Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31)

W. B. Green, M. L. Slovak, I. M. Chen, M. Pallavicini, J. L. Hecht, C. L. Willman

Research output: Contribution to journalArticlepeer-review


One allele of interferon regulatory factor-1 (IRF-1), a transcriptional activator of genes critical for growth suppression, differentiation, and apoptosis, is usually deleted in acute myeloid leukemias (AML) and myelodysplasias (MDS) with deletion of chromosome 5q31. Accelerated exon skipping of IRF-1, resulting in transcripts lacking a translation initiation site, has been hypothesized as a means of functional inactivation of IRF-1 in AML/MDS. To test this hypothesis, we developed quantitative competitive RT-PCR assays to measure levels of full length and exon-skipped IRF-1 transcripts and measured IRF-1 proteins by Western blotting in a series of 45 samples of AML (13: -5/del5(q); 11: t(15;17); 7: t(8;21); and 7: inv(16)), normal blood and marrow, and myeloid cell lines. In contrast to AMLs with inv(16) or t(8;21), two AML samples with del(5q) had accelerated exon skipping and relatively low levels of full-length transcripts, while a third sample had very low transcript levels; IRF-1 proteins were not expressed and could not be induced by interferon gamma (IFNγ). An additional six AML cases with -5/del(5q) had moderate exon-skipping and lacked constitutive IRF-1 proteins; however IRF-1 proteins were IFNγ-inducible. Unexpectedly, all primary acute promyelocytic leukemia (APL) samples lacked IRF-1 protein and most exhibited accelerated exon skipping; furthermore, IRF-1 could not be induced by IFNγ or all-trans retinoic acid (ATRA) which both induce IRF-1 in the NB4 APL cell line. Thus, accelerated exon skipping results in a loss of IRF-1 expression and function that cannot be overcome by exposure to inducing agents in a subset of AML patients with -5/del(5q) and in APL.

Original languageEnglish (US)
Pages (from-to)1960-1971
Number of pages12
Issue number12
StatePublished - 1999


  • Acute myeloid leukemia
  • Acute promyelocytic leukemia
  • Chromosome 5q
  • Exon-skipping
  • Interferon regulatory factor-1
  • t(15;17)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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