Fetal to adult hemopoietic cell transplantation in humans: insights into hemoglobin switching

A 2-year-old boy with refractory acute leukemia (ALL) was transplanted with liver cells from twin fetuses of an 18-gestational-week age. Regeneration of hemopoietic cells was evident during the second week following transplantation when a cellular, predominantly erythroid, marrow was present. Studies of bone marrow and peripheral blood cells obtained 21 days posttransplant showed that bone marrow and peripheral blood BFU-E-derived erythroblasts displayed typical fetal patterns of globin chain synthesis (gamma/gamma + beta ratios: 0.87 to 0.98). In addition, all of the individually analyzed erythroid clones displayed a fetal type of globin program, suggesting that the presence of rare, partially switched clones was unlikely. Additional evidence supported the fetal phenotype of these progenitors. The il expression of culture- derived erythroblasts was typical for fetal erythroid cells. As in fetal cells, fetal sheep serum influenced neither the globin nor the il phenotypes, and the growth characteristics were as those observed in fetal liver cultures. That these fetal progenitors matured in vivo and produced cells with a fetal program was shown by the pattern of globin biosynthesis in bone marrow cells and peripheral blood reticulocytes (gamma/gamma + beta ratios: 0.85 to 0.95) at days 14 and 21 posttransplantation. These results indicate that the transplanted fetal cells, in spite of their proliferation and differentiation in the environment of the recipient, continued to express during the early posttransplantation period fetal patterns of globin, surface antigenic determinants, and growth and response to environmental modulation. The observations in this patient support the notion that hemoglobin switching is primarily controlled by a mechanism intrinsic to the stem cell.