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Cytoprotective effects of hematopoietic growth factors on primary human acute myeloid leukemias are not mediated through changes in BCL-2, bax, or p21WAF1/CIP1.

Publication ,  Journal Article
DiGiuseppe, JA; Kastan, MB; Weng, LJ; Gore, SD
Published in: In Vivo
1999

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 p21WAF1/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 p21WAF1/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 p21WAF1/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 p21WAF1/CIP1 levels, suggesting that modulation of p21WAF1/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 p21WAF1/CIP1 protein levels.

Duke Scholars

Published In

In Vivo

ISSN

0258-851X

Publication Date

1999

Volume

13

Issue

1

Start / End Page

1 / 6

Location

Greece

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Cells, Cultured
  • Stem Cell Factor
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leukemia, Myelomonocytic, Acute
 

Published In

In Vivo

ISSN

0258-851X

Publication Date

1999

Volume

13

Issue

1

Start / End Page

1 / 6

Location

Greece

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Cells, Cultured
  • Stem Cell Factor
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leukemia, Myelomonocytic, Acute