Oxidative stress is increased in primary and post−polycythemia vera myelofibrosis
Received 4 October 2009; received in revised form 6 July 2010; accepted 9 July 2010. published online 23 July 2010. Uncorrected Proof
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.
Materials and 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.
aDipartimento di Scienze Mediche, Ematologia, Centro Trapianti di Midollo, Milan, Italy
bDipartimento di Scienze Neurologiche Centro “Dino Ferrari”, Milan, Italy
fA. Bianchi Bonomi Centro Trombosi ed Emofilia, Dipartimento di Medicina Interna e Fondazione Luigi Villa, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
Offprint requests to: Claudia Vener, M.D., Ph.D., U.O. Ematologia, Centro Trapianti di Midollo, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milano 20122, Italy
∗ Drs. Vener and Novembrino contributed equally to this work.
ABSTRACT