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Improvement of mouse beta-thalassemia by recombinant human erythropoietin
K Leroy-Viard, P Rouyer-Fessard and Y Beuzard
INSERM U 91, CNRS UA 607, Hopital Henri Mondor, Creteil, France.
Homozygous beta thalassemic mice received 50 U (1,660 U/kg) of recombinant
human erythropoietin (rhEpo) 5 days a week for 2 weeks. Hemoglobin
increased from 9.2 +/- 0.6 g/dL to 10.5 +/- 0.4 g/dL (P = .002) and
hematocrit increased from 29.2% +/- 0.9% to 34.1% +/- 1.9% (P = .0014). The
beta minor/alpha globin chain synthesis ratio increased slightly but
significantly between day -4 (0.75 +/- 0.07) and day 4 (0.81 +/- 0.04) (P =
.01) and reached a minimum ratio (0.67 +/- 0.03) on day 15 (P = .001),
being parallel to reticulocyte counts and to the incorporated
trichloracetic acid (TCA)-insoluble radioactivity, therefore parallel to
the erythropoietic output in thalassemic mice, as in normal mice.
Erythrocyte defects were improved in beta thalassemic mice treated by
rhEpo: membrane-associated alpha globin was significantly decreased (P less
than .01), thiol group reactivity of ankyrin was significantly improved (P
less than .05), spectrin alterations were reduced, and deformability of
mouse thalassemic red blood cells was normalized. These results provide
experimental criteria for modulating globin chain imbalance necessary for
the therapy of human beta thalassemia intermedia, and suggest that rhEpo
might be of interest to improve the red blood cell mass and reduce
erythrocyte alterations in this disease.
Volume 78,
Issue 6,
pp. 1596-1602,
09/15/1991
Copyright © 1991 by The American Society of Hematology
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