title: Cytoprotective effects of hematopoietic growth factors on primary human acute myeloid leukemias are not mediated through changes in BCL-2, bax, or p21WAF1/CIP1.
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 p21WAF1/CIP1 in cell lines, few data address whether HGF regulate the expression of these proteins in primary acute myeloid leukemia (AML).
  
  
  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.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8963, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: DiGiuseppe
authors.forename: M B
authors.initials: MB
authors.lastname: Kastan
authors.forename: L J
authors.initials: LJ
authors.lastname: Weng
authors.forename: S D
authors.initials: SD
authors.lastname: Gore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000378:metabolism*; D015479:Leukemia, Myelomonocytic, Acute / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D051028:bcl-2-Associated X Protein; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor