|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3589-3593
Acquired DNA mutations associated with in vivo hydroxyurea
exposure
Valerie N. Hanft,
Steven R. Fruchtman,
Chrisley V. Pickens,
Wendell F. Rosse,
Thad A. Howard, and
Russell E. Ware
From the Division of Hematology/Oncology, Department of Pediatrics,
and the Division of Hematology, Department of Medicine, Duke University
Medical Center, Durham, NC, and the Bone Marrow Transplantation
Program, Mt Sinai Medical Center, New York, NY.
Hydroxyurea (HU) is an effective therapeutic agent for patients with
myeloproliferative disorders (MPDs) or sickle cell disease (SCD).
Short-term HU toxicities primarily include transient myelosuppression, but long-term HU risks have not been defined. The mutagenic and carcinogenic potential of HU is not established, although HU has been
associated with an increased risk of leukemia in some patients with
MPD. In this study, 2 assays were used to quantitate acquired somatic
DNA mutations in peripheral blood mononuclear cells (PBMCs) after in
vivo HU exposure. The HPRT assay measures hypoxanthine phosphoribosyl
transferase (hprt) mutations, while the VDJ
assay identifies "illegitimate" T-cell receptor V -J
interlocus recombination events. PBMCs were analyzed from patients with
MPD, adults and children with SCD, and normal controls. MPD patients
with prolonged HU exposure had numbers of DNA mutations equivalent to
patients with low HU exposure or controls. Similarly, adults with SCD
had equivalent numbers of DNA mutations regardless of HU exposure. Children with SCD and 30-month HU exposure had equivalent
hprt mutations but significantly more VDJ
mutations (1.82 ± 1.20 events per µg DNA) than children with
7-month HU exposure (1.58 ± 0.87 events) or no HU exposure
(1.06 ± 0.45 events), P = .04 by analysis of variance.
Taken together, these data suggest that the mutagenic and carcinogenic
potential of in vivo HU therapy is low. Although increased numbers of
illegitimate VDJ recombination events do not directly portend leukemia,
young patients with SCD and HU exposure should be monitored serially
for increases in DNA mutations.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Arana-Yi, A. Quintas-Cardama, F. Giles, D. Thomas, A. Carrasco-Yalan, J. Cortes, H. Kantarjian, and S. Verstovsek
Advances in the Therapy of Chronic Idiopathic Myelofibrosis
Oncologist,
September 1, 2006;
11(8):
929 - 943.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Burkitt and A. Raafat
Nitric oxide generation from hydroxyurea: significance and implications for leukemogenesis in the management of myeloproliferative disorders
Blood,
March 15, 2006;
107(6):
2219 - 2222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-S. Chim, Y.-L. Kwong, A. K.-W. Lie, S.-K. Ma, C.-C. Chan, L.-G. Wong, B. C. San Kho, H.-K. Lee, J. P.-Y. Sim, C.-H. Chan, et al.
Long-term Outcome of 231 Patients With Essential Thrombocythemia: Prognostic Factors for Thrombosis, Bleeding, Myelofibrosis, and Leukemia
Arch Intern Med,
December 12, 2005;
165(22):
2651 - 2658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Coller
Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality: Is It Time to Intervene?
Arterioscler. Thromb. Vasc. Biol.,
April 1, 2005;
25(4):
658 - 670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Gulbis, D. Haberman, D. Dufour, C. Christophe, C. Vermylen, F. Kagambega, F. Corazza, C. Devalck, M.-F. Dresse, K. Hunninck, et al.
Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience
Blood,
April 1, 2005;
105(7):
2685 - 2690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Campbell and A. R. Green
Management of Polycythemia Vera and Essential Thrombocythemia
Hematology,
January 1, 2005;
2005(1):
201 - 208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. Harrison
Platelets and Thrombosis in Myeloproliferative Diseases
Hematology,
January 1, 2005;
2005(1):
409 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Schafer
Thrombocytosis
N. Engl. J. Med.,
March 18, 2004;
350(12):
1211 - 1219.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Zimmerman, W. H. Schultz, J. S. Davis, C. V. Pickens, N. A. Mortier, T. A. Howard, and R. E. Ware
Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease
Blood,
March 15, 2004;
103(6):
2039 - 2045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Spivak, G. Barosi, G. Tognoni, T. Barbui, G. Finazzi, R. Marchioli, and M. Marchetti
Chronic Myeloproliferative Disorders
Hematology,
January 1, 2003;
2003(1):
200 - 224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Horikawa, T. Kawaguchi, S. Ishihara, S. Nagakura, M. Hidaka, T. Kagimoto, H. Mitsuya, and H. Nakakuma
Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria
Blood,
January 1, 2002;
99(1):
24 - 29.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Storen and A. Tefferi
Long-term use of anagrelide in young patients with essential thrombocythemia
Blood,
February 15, 2001;
97(4):
863 - 866.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
