Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia

Research output: Contribution to journalArticlepeer-review

Abstract

Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle arrest, apoptosis, and clinical responses in selected patients with acute myeloid leukemia (AML). A better understanding of the molecular pathways targeted by flavopiridol is needed to design optimal combinatorial therapy. Here, we report that in vivo administration of flavopiridol induced expression of the BCL-2 anti-apoptotic gene in leukemic blasts from adult patients with refractory AML. Moreover, flavopiridol repressed the expression of genes encoding oncogenic transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA Polymerase II. Our results provide mechanistic insight into the cellular pathways targeted by flavopiridol. Although further studies are needed, our findings also suggest that blocking anti-apoptotic pathways could enhance cytotoxicity with flavopiridol.

Original languageEnglish (US)
Pages (from-to)1999-2006
Number of pages8
JournalLeukemia and Lymphoma
Volume52
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • BCL-2
  • E2F1
  • Flavopiridol
  • HMGA1
  • STAT3
  • acute myeloid leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this