|
|
 Previous Article | Table of Contents | Next Article 
Hydroxyurea induction of hemoglobin F production in sickle cell disease:
relationship between cytotoxicity and F cell production
GJ Dover, RK Humphries, JG Moore, TJ Ley, NS Young, S Charache and AW Nienhuis
Initial alterations in fetal hemoglobin (HbF) production among eight sickle
cell anemia subjects treated with hydroxyurea (Hu) are summarized. Four of
these subjects had been previously treated with 5- azacytidine (5-aza). All
subjects treated with Hu (50 mg/kg/d for three to five days) had
suppression of their total reticulocyte counts by seven days, whereas the
four subjects previously treated with 5-aza (2 mg/kg/d for three to five
days) had increased reticulocyte counts at day 7. The effect of Hu on
increasing the number of HbF-containing reticulocytes (F reticulocytes) is
extremely variable, ranging from ten- to less than onefold differences in
maximal posttherapy v pretherapy levels. Recovery from marrow suppression
did not result in greater than twofold increases in F reticulocyte counts.
Mean day 7 F reticulocyte levels in the four subjects treated with both Hu
and 5-aza were 4.1 X 10/microL and 15.4 X 10(4)/microL, respectively. Among
Hu-treated subjects, increased F reticulocyte production was correlated
with low serum creatinine levels and rapid removal of Hu from the plasma.
Furthermore, suppression of CFU-E colony formation on day 2 of therapy with
Hu was inversely correlated with maximal F reticulocyte response. We
conclude that where Hu treatment results in marrow toxicity (decreased
reticulocyte counts, decreased CFU-E colony formation) HbF production is
less likely to increase. Those sickle cell anemia subjects with minimal
renal dysfunction (serum creatinine level, greater than 1.0 mg/dL) exhibit
the most cytotoxicity and least F reticulocyte response to Hu.
Volume 67,
Issue 3,
pp. 735-738,
03/01/1986
Copyright © 1986 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J.-H. Yan, K. Ataga, S. Kaul, J. S. Olson, D. M. Grasela, S. Gothelf, A. Kutlar, and E. Orringer
The Influence of Renal Function on Hydroxyurea Pharmacokinetics in Adults With Sickle Cell Disease
J. Clin. Pharmacol.,
April 1, 2005;
45(4):
434 - 445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Vadolas, H. Wardan, M. Orford, R. Williamson, and P. A. Ioannou
Cellular genomic reporter assays for screening and evaluation of inducers of fetal hemoglobin
Hum. Mol. Genet.,
January 15, 2004;
13(2):
223 - 233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Weiner and C. Brugnara
Hydroxyurea and Sickle Cell Disease: A Chance for Every Patient
JAMA,
April 2, 2003;
289(13):
1692 - 1694.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikuta, S. Ausenda, and M. D. Cappellini
Mechanism for fetal globin gene expression: Role of the soluble guanylate cyclase-cGMP-dependent protein kinase pathway
PNAS,
February 1, 2001;
(2001)
41599798.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. F. Atweh, M. Sutton, I. Nassif, V. Boosalis, G. J. Dover, S. Wallenstein, E. Wright, L. McMahon, G. Stamatoyannopoulos, D. V. Faller, et al.
Sustained Induction of Fetal Hemoglobin by Pulse Butyrate Therapy in Sickle Cell Disease
Blood,
March 15, 1999;
93(6):
1790 - 1797.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikuta, Y. W. Kan, P. S. Swerdlow, D. V. Faller, and S. P. Perrine
Alterations in Protein-DNA Interactions in the gamma -Globin Gene Promoter in Response to Butyrate Therapy
Blood,
October 15, 1998;
92(8):
2924 - 2933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. F. Bunn
Pathogenesis and Treatment of Sickle Cell Disease
N. Engl. J. Med.,
September 11, 1997;
337(11):
762 - 769.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Steinberg, Z.-H. Lu, F. B. Barton, M. L. Terrin, S. Charache, G. J. Dover, and the Multicenter Study of Hydroxyurea
Fetal Hemoglobin in Sickle Cell Anemia: Determinants of Response to Hydroxyurea
Blood,
February 1, 1997;
89(3):
1078 - 1088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Sher, G. D. Ginder, J. Little, S. Yang, G. J. Dover, and N. F. Olivieri
Extended Therapy with Intravenous Arginine Butyrate in Patients with {beta}-Hemoglobinopathies
N. Engl. J. Med.,
June 15, 1995;
332(24):
1606 - 1610.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. P. Rodgers, G. J. Dover, N. Uyesaka, C. T. Noguchi, A. N. Schechter, and A. W. Nienhuis
Augmentation by Erythropoietin of the Fetal-Hemoglobin Response to Hydroxyurea in Sickle Cell Disease
N. Engl. J. Med.,
January 14, 1993;
328(2):
73 - 80.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. P. Perrine, G. D. Ginder, D. V. Faller, G. H. Dover, T. Ikuta, H. E. Witkowska, S.-p. Cai, E. P. Vichinsky, and N. F. Olivieri
A Short-Term Trial of Butyrate to Stimulate Fetal-Globin-Gene Expression in the {beta}-Globin Disorders
N. Engl. J. Med.,
January 14, 1993;
328(2):
81 - 86.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. P. Rodgers
Recent Approaches to the Treatment of Sickle Cell Anemia
JAMA,
April 24, 1991;
265(16):
2097 - 2101.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. Yang, Y. Kawai, R. W. Hanson, and I. J. Arinze
Sodium Butyrate Induces Transcription from the Galpha i2 Gene Promoter through Multiple Sp1 Sites in the Promoter and by Activating the MEK-ERK Signal Transduction Pathway
J. Biol. Chem.,
July 6, 2001;
276(28):
25742 - 25752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikuta, S. Ausenda, and M. D. Cappellini
Mechanism for fetal globin gene expression: Role of the soluble guanylate cyclase-cGMP-dependent protein kinase pathway
PNAS,
February 13, 2001;
98(4):
1847 - 1852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
