title: Differential expression of transforming growth factor-beta, basic fibroblast growth factor, and their receptors in CD34+ hematopoietic progenitor cells from patients with myelofibrosis and myeloid metaplasia.
abstract: Myelofibrosis with myeloid metaplasia (MMM) is a myeloproliferative disorder characterized by clonal expansion of hematopoiesis and marrow fibrosis. Previous results from our group have shown an increased production of two potent fibrogenic factors also involved in the regulation of primitive hematopoietic cells, namely transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF), in patients with MMM. It is likely to assume that the myeloproliferation characteristic of this disease may result from an abnormal proliferation of CD34+ hematopoietic progenitors. Thus, we were particularly concerned in studying the gene and protein expression of these cytokines and their receptors in CD34+ progenitors purified from the peripheral blood of MMM patients by using semiquantitative reverse transcriptase-polymerase chain reaction and immunolabeling methods. Our data showed that the expression of TGF-beta1 is not altered in patients CD34+ cells; in contrast, the expression of TGF-beta type II receptor is significantly decreased in such cells, as compared with CD34+ cells from healthy subjects. Regarding bFGF, the very low expression of the cytokine and its type I and II receptors detected in normal CD34+ cells contrasts with that observed in patients' CD34+ cells, which is significantly higher. Our results might be a clue for a better understanding of the mechanism(s) involved in the dysregulation of hematopoiesis in MMM. Actually, the increased expression of bFGF and its receptors associated with the reduction of the TGF-beta binding receptor in CD34+ progenitors from MMM patients might facilitate the expansion of hematopoietic progenitors, not only by stimulating their growth and/or survival, but also by overcoming negative regulatory signals.
authors.affiliation: INSERM U268, Hôpital Paul Brousse, Villejuif, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Le Bousse-Kerdilès
authors.forename: S
authors.initials: S
authors.lastname: Chevillard
authors.forename: A
authors.initials: A
authors.lastname: Charpentier
authors.forename: N
authors.initials: N
authors.lastname: Romquin
authors.forename: D
authors.initials: D
authors.lastname: Clay
authors.forename: F
authors.initials: F
authors.lastname: Smadja-Joffe
authors.forename: V
authors.initials: V
authors.lastname: Praloran
authors.forename: B
authors.initials: B
authors.lastname: Dupriez
authors.forename: J L
authors.initials: JL
authors.lastname: Demory
authors.forename: C
authors.initials: C
authors.lastname: Jasmin
authors.forename: M C
authors.initials: MC
authors.lastname: Martyré
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000032:analysis* / Q000097:blood; D000943:Antigens, Differentiation / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000097:blood; D055728:Primary Myelofibrosis / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D063268:Sialic Acid Binding Ig-like Lectin 3; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D063268:Sialic Acid Binding Ig-like Lectin 3; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1