Cytoprotective effects of hematopoietic growth factors on primary human acute myeloid leukemias are not mediated through changes in BCL-2, BAX, or p21(WAF1/CIP1)

Joseph A. Digiuseppe, Michael B. Kastan, Li Jun Weng, Steven D. Gore

Research output: Contribution to journalArticle

Abstract

Background: Hematopoietic growth factors (HGF) can suppress chemotherapy-induced programmed cell death (apoptosis) in hematopoietic cells. Although HGF can modulate the expression of apoptosis-regulatory genes, including bcl-2, bax, and p21(WAF1/CIP1) in cell lines, few data address whether HGF regulate the expression of these proteins in primary acute myeloid leukemia (AML). Materials and Methods: We evaluated the expression of bcl-2, bax, and p21(WAF1/CIP1) in primary samples from patients with AML in the presence and absence of HGF. The potential association of HGF-induced changes in the levels of these proteins with inhibition of chemotherapy-induced apoptosis was further investigated. Results: While a combination of steel factor (SF) and PIXY321 inhibited etoposide-induced apoptosis in 8/11 primary AML samples studied, Bcl-2 and bax protein levels were unaffected by exposure to HGF and/or etoposide. In contrast, HGF enhanced basal and etoposide-induced p21(WAF1/CIP1) protein levels in 9/11 and 7/11 of the cases, respectively. In several cases, inhibition of apoptosis by HGF was seen without up-regulation of p21(WAF1/CIP1) levels, suggesting that modulation of p21(WAF1/CIP1) is not required for HGF-mediated inhibition of apoptosis. Conclusions: These data indicate that HGF-mediated inhibition of chemotherapy-induced apoptosis in primary AML samples is not mediated through changes in Bcl-2, bax, and p21(WAF1/CIP1) protein levels.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalIn Vivo
Volume13
Issue number1
StatePublished - Jan 1 1999

Keywords

  • Acute myeloid leukemia
  • Apoptosis
  • Growth factors
  • bax
  • bcl-2
  • p21(WAF1/CIP1)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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