title: Oxidative stress is increased in primary and post-polycythemia vera myelofibrosis.
abstract: OBJECTIVE
  To determine if increased cell turnover in chronic myeloproliferative disorders can lead to hyperhomocysteinemia as a result of folate and/or cobalamin depletion, and contribute to oxidative stress.
  
  
  METHODS
  The clinical role of oxidative stress was investigated by measuring reactive oxygen species (ROS), total antioxidant capacity (TAC), and total homocysteine (tHcy), folate, cobalamin, and holotranscobalamin (HoloTC) levels in 51 chronic myeloproliferative disorders patients (male-to-female ratio: 1.1; median age: 64 years; range, 40-84 years), including 42 with primary myelofibrosis and 9 with post-polycythemia vera myelofibrosis.
  
  
  RESULTS
  Myelofibrotic patients had higher tHcy (p = 0.0201) and an unbalanced oxidative status (higher ROS and lower TAC levels; p < 0.0001) than controls. Presence of diabetes or another neoplasia was associated with higher ROS levels (p < 0.05), splenomegaly, hepatomegaly, and peripheral blasts with lower HoloTC levels (p < 0.005). The most severe forms of myelofibrosis (2-3) were associated with lower TAC (p = 0.045) and HoloTC levels (p = 0.017). Patients with Janus kinase-2 mutations had lower HoloTC levels (p = 0.0059). HoloTC deficiency was more frequently associated with Janus kinase-2 homozygosity (p < 0.0003).
  
  
  CONCLUSIONS
  Our findings suggest that the determination of HoloTC, tHcy, ROS concentrations, and TAC, can identify latent cobalamin deficiency and provide a rational basis for correcting the increased oxidation associated with disease progression.
authors.affiliation: Dipartimento di Scienze Mediche, Ematologia, Centro Trapianti di Midollo, Milan, Italy. claudiavener@tiscali.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Vener
authors.forename: Cristina
authors.initials: C
authors.lastname: Novembrino
authors.forename: Fabrizia Bamonti
authors.initials: FB
authors.lastname: Catena
authors.forename: Nicola Stefano
authors.initials: NS
authors.lastname: Fracchiolla
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
authors.forename: Federica
authors.initials: F
authors.lastname: Savi
authors.forename: Franca
authors.initials: F
authors.lastname: Radaelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Fermo
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonati
authors.forename: Marzia
authors.initials: M
authors.lastname: Menegatti
authors.forename: Giorgio Lambertenghi
authors.initials: GL
authors.lastname: Deliliers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D018384:Oxidative Stress; D011087:Polycythemia Vera / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014155:Transcobalamins / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014155:Transcobalamins; D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D053614:Janus Kinase 2; D014805:Vitamin B 12