title: Increased leucocyte apoptosis in transfused β-thalassaemia patients.
abstract: This exploratory study assessed apoptosis in peripheral blood leucocytes (PBL) from β-thalassaemia patients receiving chronic transfusions and chelation therapy (deferasirox or deferoxamine) at baseline, 1, 6, and 12 months. At baseline, thalassaemic PBLs presented 50% greater levels of Bax (BAX), 75% higher caspase-3/7, 48% higher caspase-8 and 88% higher caspase-9 activities and 428% more nucleosomal DNA fragmentation than control subjects. Only neutrophils correlated significantly with apoptotic markers. Previously, we showed that over the treatment year, hepatic iron declined; we now show that the ratio of Bax/Bcl-2 (BCL2), (-27·3%/year), and caspase-9 activity (-13·3%/year) declined in both treatment groups, suggesting that chelation decreases body iron and indicators of PBL apoptosis.
authors.affiliation: Children's Hospital & Research Center Oakland, Oakland, CA 94609, USA.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Walter
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.forename: Janet L
authors.initials: JL
authors.lastname: Kwiatkowski
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: Thomas
authors.initials: T
authors.lastname: Coates
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Giardina
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grady
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: Felicia
authors.initials: F
authors.lastname: Trachtenberg
authors.forename: Daniele
authors.initials: D
authors.lastname: Alberti
authors.forename: Ellen
authors.initials: E
authors.lastname: Fung
authors.forename: Bruce
authors.initials: B
authors.lastname: Ames
authors.forename: Annie
authors.initials: A
authors.lastname: Higa
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001803:Blood Transfusion; D020169:Caspases / Q000378:metabolism; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D017086:beta-Thalassemia / Q000378:metabolism* / Q000628:therapy
chemical_list: D051028:bcl-2-Associated X Protein; D020169:Caspases