Marrow Transplantation in the Treatment of a Murine Heritable Hemolytic Anemia

• Published in: Blood 1989-05, Vol.73 (7), p.2014-2017
• Main Authors: Barker, Jane E., McFarland-Starr, Eleanor C.
• Format: Article
• Language: English
• Subjects: Anemia, Hemolytic, Congenital - blood; Anemia, Hemolytic, Congenital - genetics; Anemia, Hemolytic, Congenital - surgery; Anemias. Hemoglobinopathies; Animals; Biological and medical sciences; Bone Marrow - pathology; Bone Marrow - radiation effects; Bone Marrow Transplantation; Diseases of red blood cells; Erythrocyte Count - radiation effects; Glucose-6-Phosphate Isomerase - blood; Glucose-6-Phosphate Isomerase - genetics; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - pathology; Male; Medical sciences; Mice; Mice, Mutant Strains - blood; Phenotype; Postoperative Complications - blood; Postoperative Complications - pathology; Radiation Chimera
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V73.7.2014.2014

Mice with hemolytic anemia, sphha/sphha, have extremely fragile RBCs with a lifespan of approximately one day. Neither splenectomy nor simple transplantation of normal marrow after lethal irradiation cures the anemia but instead causes rapid deterioration and death of the mutant unless additional prophylactic procedures are used. In this report, we show that normal marrow transplantation preceded by sublethal irradiation increases but does not normalize RBC count. The mutant RBCs but not all the WBCs are replaced by donor cells. Splenectomy of the improved recipient causes a dramatic decrease in RBC count, indicating that the mutant spleen is a site of donor-origin erythropoiesis as well as of RBC destruction. Injections of iron dextran did not improve RBC counts. Transplantation of primary recipient marow cells into a secondary host with a heritable stem cell deficiency (W/ Wv) corrects the defect caused by residence of the normal cells in the sphha/sphha host. The original + / + donor cells replace the RBCs of the secondary host, and the RBC count is normalized. Results indicate that the environment in the sphha/sphha host is detrimental to normal (as well as mutant) erythroid cells but the restriction is not transmitted.