Oxidative stress is increased in primary and post-polycythemia vera myelofibrosis.
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.
Vener
Claudia
C
Dipartimento di Scienze Mediche, Ematologia, Centro Trapianti di Midollo, Milan, Italy. claudiavener@tiscali.it
Novembrino
Cristina
C
Catena
Fabrizia Bamonti
FB
Fracchiolla
Nicola Stefano
NS
Gianelli
Umberto
U
Savi
Federica
F
Radaelli
Franca
F
Fermo
Elisa
E
Cortelezzi
Agostino
A
Lonati
Silvia
S
Menegatti
Marzia
M
Deliliers
Giorgio Lambertenghi
GL
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
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