title: Factors regulating Hb F synthesis in thalassemic diseases.
abstract: BACKGROUND: The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo) and Hb F, between Hb F and point mutations of the gamma gene promoters. MATERIALS AND METHODS: Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. RESULTS: Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta degrees or severe beta+ thal mutations are associated with evident beta thal int (88%) and almost invariably (98%) with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo) level. The mutation Ggamma -158 C&RightArrow;T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. CONCLUSIONS: The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C&RightArrow;T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients.
authors.affiliation: Associazione Nazionale per la lotta contro Ie Microcitemie in Italia, Rome, Italy. ibianco@tin.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mastropietro
authors.forename: Guido
authors.initials: G
authors.lastname: Modiano
authors.forename: Maria
authors.initials: M
authors.lastname: Cappabianca
authors.forename: Enrica
authors.initials: E
authors.lastname: Foglietta
authors.forename: Carmelo
authors.initials: C
authors.lastname: D'Asero
authors.forename: Mauro
authors.initials: M
authors.lastname: Mezzabotta
authors.forename: Donatella
authors.initials: D
authors.lastname: Ponzini
authors.forename: Laura
authors.initials: L
authors.lastname: Maffei
authors.forename: Antonio
authors.initials: A
authors.lastname: Amato
authors.forename: Maria
authors.initials: M
authors.lastname: Lerone
authors.forename: Paola
authors.initials: P
authors.lastname: Grisanti
authors.forename: Paola
authors.initials: P
authors.lastname: Di Biagio
authors.forename: Silvana
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Ida
authors.initials: I
authors.lastname: Bianco