title: Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet-derived transforming growth factor beta 1, produced in normal amount, in patients with essential thrombocythaemia.
abstract: In this study we evaluated the amount of transforming growth factor-beta 1 (TGF-beta 1) in platelet lysates obtained from 12 patients affected by essential thrombocythaemia (ET) in comparison with five patients affected by myelofibrosis with myeloid metaplasia (MMM) and 15 healthy donors. The levels of both bioactive and latent TGF-beta 1, evaluated in a bioassay on CCL64 cells, before and after transient acidification, were similar in platelet lysates from ET patients and normal donors and significantly (P < 0.01) elevated in platelet lysates from MMM patients. Moreover, platelet lysates from ET patients and normal controls, showed a similar degree of colony suppression when tested on haematopoietic progenitor (CD34+) cells, purified from normal bone marrows, whereas platelet lysates from MMM patients showed a higher (P < 0.01) inhibitory activity on normal CFU-meg and BFU-E growth. In parallel, platelet lysates form ET patients and normal controls were tested on CD34+ cells, purified from ET bone marrows. ET bone marrow BFU-E, similarly to normal bone marrow BFU-E, were markedly inhibited by platelet lysates, whereas ET bone marrow CFU-meg were significantly (P < 0.05) less responsive to the inhibitory activity of platelet lysates than normal bone marrow CFU-meg. The main factor responsible for the inhibitory activity contained in platelet lysates was transforming growth factor-beta 1 (TGF-beta 1), as demonstrated by the ability of a polyclonal neutralizing anti-TGF-beta 1 antibody to almost completely reverse the suppressive effect of platelet lysates on CFU-meg and BFU-E growth. Our data demonstrate that the amount of intraplatelet TGF-beta 1 is similar in ET patients and normal controls, whereas it is increased in platelets from MMM patients. Moreover, megakaryocyte progenitors in ET show a reduced sensitivity to platelet-derived inhibitors and, in particular, to TGF-beta 1.
authors.affiliation: Institute of Human Anatomy, University of Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zauli
authors.forename: G
authors.initials: G
authors.lastname: Visani
authors.forename: L
authors.initials: L
authors.lastname: Catani
authors.forename: N
authors.initials: N
authors.lastname: Vianelli
authors.forename: L
authors.initials: L
authors.lastname: Gugliotta
authors.forename: S
authors.initials: S
authors.lastname: Capitani
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000097:blood; D013920:Thrombocythemia, Essential / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000494:pharmacology
chemical_list: D016212:Transforming Growth Factor beta