title: Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia.
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.
authors: Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Dwella M
authors: DM
authors: Nelson
authors: Biju
authors: B
authors: Joseph
authors: Joelle
authors: J
authors: Hillion
authors: Jodi
authors: J
authors: Segal
authors: Judith E
authors: JE
authors: Karp
authors: Linda M S
authors: LM
authors: Resar
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001752:Blast Crisis / Q000188:drug therapy; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects*; D012319:RNA Polymerase II / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C077990:alvocidib; D012319:RNA Polymerase II