The geldanamycin derivative 17-AAG decreases VEGF secretion and leukemia growth support by trisomy 8 myelodysplastic syndrome bone marrow stromal cells.
Stromal cells from a child with constitutional trisomy 8 who developed myelodysplastic syndrome (MDS) were found to produce abnormal levels of various cytokines, including VEGF, and supported the growth of leukemic cells in co-culture assays. This study shows that the geldanamycin derivative 17-AAG effectively reduces the VEGF expression by MDS stromal cells. In co-culture experiments this agent also blocks the ability of the MDS stromal cells to stimulate the growth of leukemic cells. These data provide important initial evidence for the effect of 17-AAG on the marrow microenvironment and its potential use in the treatment of MDS and leukemia.
Hawkins
Lindsay M
LM
Southern Alberta Children's Cancer Program, Alberta Children's Hospital Calgary Alberta Canada.
Narendran
Aru
A
D016227:Benzoquinones; D001854:Bone Marrow Cells / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D002898:Chromosomes, Human, Pair 8; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis / Q000187:drug effects; D005260:Female; D006801:Humans; D047029:Lactams, Macrocyclic; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019899:Paracrine Communication / Q000187:drug effects; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects* / Q000473:pathology; D014314:Trisomy; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000378:metabolism
D016227:Benzoquinones; D016207:Cytokines; D047029:Lactams, Macrocyclic; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017828:Rifabutin; C112765:tanespimycin