Fetal to adult hemopoietic cell transplantation in humans: insights into
hemoglobin switching
T Papayannopoulou, B Nakamoto, F Agostinelli, M Manna, G Lucarelli and G Stamatoyannopoulos
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.
Volume 67,
Issue 1,
pp. 99-104,
01/01/1986
Copyright © 1986 by The American Society of Hematology
