title: The angioregulatory phenotype of native human acute myelogenous leukemia cells: influence of karyotype, Flt3 abnormalities and differentiation status.
abstract: BACKGROUND
  The cytogenetic abnormalities and the response to induction therapy have been regarded as the most important prognostic parameters in acute myelogenous leukemia (AML) patients. Recent studies have demonstrated that internal tandem duplications and specific D-835 point mutations of the Flt3 gene, as well as the angioregulatory phenotype represent additional adverse prognostic factors. The aim of the study was to investigate possible associations between genetic abnormalities, differentiation status and angioregulatory phenotype in native human AML blasts.
  
  
  METHODS
  Native AML blasts derived from consecutive patients were cultured in vitro and concentrations of angioregulatory molecules determined in the supernatants.
  
  
  RESULTS
  Most patients released at least two different angioregulatory mediators. Pro-angiogenic interleukin 8 (IL8) was released at relatively high levels for most patients, many of these patients showed additional release of pro-angiogenic vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). High release of anti-angiogenic IL12 was associated with high release of pro-angiogenic IL8 and VEGF. Furthermore, patients with D-835 mutations showed increased IL12 release, whereas patients with normal karyotype had decreased HGF release. Myelomonocytic differentiation was associated with IL18 release and CD34 expression with low IL12 release.
  
  
  CONCLUSIONS
  Our results suggest that native human AML blasts have a pro-angiogenic phenotype. Although the investigated genetic abnormalities are associated with variation in the in vitro release of angioregulators, these differences are relatively small and do not quantitatively involve the most important IL8 release. It therefore seems unlikely that this phenotypic variation can explain the prognostic impact of the genetic abnormalities.
authors.affiliation: Section for Hematology, Department of Medicine, Haukeland University Hospital and the University of Bergen, Bergen, Norway. nils.idar.glenjen@helse-bergen.no
authors.forename: Nils
authors.initials: N
authors.lastname: Glenjen
authors.forename: Randi
authors.initials: R
authors.lastname: Hovland
authors.forename: Line
authors.initials: L
authors.lastname: Wergeland
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Wendelbo
authors.forename: Peter
authors.initials: P
authors.lastname: Ernst
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007621:Karyotyping; D020738:Leptin / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D018952:Antigens, CD34; D043169:Endostatins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D016209:Interleukin-8; D020738:Leptin; D008222:Lymphokines; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D018664:Interleukin-12; D017228:Hepatocyte Growth Factor; D003094:Collagen; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3