title: Carboxy-terminal fragment of osteogenic growth peptide in vitro increases bone marrow cell density in idiopathic myelofibrosis.
abstract: Idiopathic myelofibrosis (IMF) is a clonal stem cell disorder characterized by reactive fibrosis of bone marrow sustained by a complex cytokine network. At present, no efficacious therapy for this disease exists. Synthetic carboxy-terminal pentapeptide of osteogenic growth factor (sOGP10-14) can increase bone marrow cellularity and the number of haematopoietic colonies; this study evaluated the activity of sOGP10-14 in IMF. Fragments of bone marrow biopsies from patients affected by IMF were cultured with or without the addition of sOGP10-14. Cellular density was evaluated by image analysis, and transforming growth factor-beta1 (TGF-beta1) concentration was immunologically assayed in the supernatant of cultured bone marrow biopsies. The proliferation rate of the megakaryoblastic M07-e cell line, cultured in the presence of either granulocyte-macrophage colony stimulating factor or thrombopoietin (TPO), and with or without sOGP10-14, was evaluated. Megakaryocyte colony forming unit (CFU-Mk) assay was performed on bone marrow samples of IMF patients with or without sOGP10-14. After 14 d, bone marrow cellularity was significantly increased in samples cultured with the pentapeptide. Moreover, sOGP10-14 induced a significant increase of TGF-beta in culture supernatants. TPO-primed proliferation of M07-e was reduced by sOGP10-14, and the pentapeptide significantly reduced CFU-Mk on IMF bone-marrow-derived cells. sOGP10-14 increased ex vivo bone marrow cellularity in IMF. This action could be related to the megakaryocyte inhibition induced by the interference of this pentapeptide with growth factor activities. These findings suggest that a deficiency of osteoblast-related factors may play a role in bone marrow failure in IMF.
authors.affiliation: Department of Oncology, Transplants and Advanced Technologies in Medicine, Haematology Division, University of Pisa, Via Roma 67, 56100 Pisa, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Fazzi
authors.forename: Simone
authors.initials: S
authors.lastname: Pacini
authors.forename: Rossana
authors.initials: R
authors.lastname: Testi
authors.forename: Antonio
authors.initials: A
authors.lastname: Azzarà
authors.forename: Sara
authors.initials: S
authors.lastname: Galimberti
authors.forename: Cesarina
authors.initials: C
authors.lastname: Testi
authors.forename: Luisa
authors.initials: L
authors.lastname: Trombi
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Metelli
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004723:Endorphins / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D055728:Primary Myelofibrosis / Q000473:pathology*; D013926:Thrombopoietin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D004723:Endorphins; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C050198:historphin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin