The biology and treatment of acute progranulocytic leukemia

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Acute progranulocytic leukemia (APL) is one of the most curable of all human cancers. Combination treatment with retinoic acid (RA) and anthracycline-based chemotherapy is safe and effective for the vast majority of patients, and several novel treatment approaches are under investigation for high-risk or relapsed patients. The APL-specific oncogenes PML-RARα and PLZF-RARα both bind nuclear corepressors and recruit histone deacetylase activity to promoters of RA target genes. The differential sensitivity of binding of these oncogenes to nuclear corepressors in the presence of RA appears to explain the resistance of PLZF-RARα-related APL to RA and at the same time explains the effectiveness of RA in PML-RARα-positive APL. Transcriptional repression of RA target genes, mediated by histone deacetylase activity, may thus be a key pathogenetic event in APL. Cure of the minority of resistant patients requires further refinement of current treatment approaches and appropriately timed incorporation of novel therapies, such as arsenic trioxide or histone deacetylase inhibitors.

Original languageEnglish (US)
Pages (from-to)9-13
Number of pages5
JournalCurrent Opinion in Oncology
Volume11
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

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Acute Promyelocytic Leukemia
Tretinoin
Co-Repressor Proteins
Histone Deacetylases
Oncogenes
Therapeutics
Histone Deacetylase Inhibitors
Anthracyclines
Genes
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

The biology and treatment of acute progranulocytic leukemia. / Slack, James L.

In: Current Opinion in Oncology, Vol. 11, No. 1, 1999, p. 9-13.

Research output: Contribution to journalArticle

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