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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4432-4439. Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-10-3705.
Submitted October 30, 2003
Hematology/Medicine, University of Washington, Seattle, WA, USA * Corresponding author; email: rrichard{at}u.washington.edu.
In vivo selection may provide a means to increase the relative number of cells of donor origin in the setting of hemopoietic chimerism. We have tested whether in vivo selection using chemical inducers of dimerization (CID) can direct the expansion of transduced normal donor erythrocytes in the setting of chimerism using a mouse model of pyruvate kinase deficiency. Marrow cells from normal CBA/N mice were transduced with a vector (F36Vmpl) that promotes cell growth in the presence of CID. Transduced cells were then transplanted into minimally conditioned, pyruvate kinase deficient, recipients (CBA-Pk-1slc/Pk-1slc) to establish stable chimerism. CID administration resulted in expansion of normal donor erythrocytes and improvement of the anemia. The preferential expansion of normal erythrocytes also resulted in a decrease in erythropoietin levels, reducing the drive for production of pyruvate kinase deficient red cells. CID-mediated expansion of genetically modified erythrocytes could prove a useful adjunct to transplant methods that achieve erythroid chimerism.
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