Ontogeny of Erythropoiesis After Bone Marrow Ablation and Allogeneic Bone Marrow Grafting

H UMAN and several other mammalian species sequentially express different globin genes during ontogeny, or during periods of “stress,” such as hypoxemia or anemia. Hemoglobin ontogeny in humans includes three distinct phases. The “embryonic” phase predominates from the 5th to the 16th week of gestation. In this period, embryonic hemoglobin chains are and . Throughout the remainder of gestation (“fetal” phase), the major hemoglobin is hemoglobin-F (a2’y2), but gradually increasing amounts of HbA (a fl2) can be detected during this phase. After birth, fetal hemoglobin is gradually replaced by adult hemoglobin (HbA), and HbF represents approximately 1% of the total hemoglobin (“adult” phase). Residual hemoglobin-F contains two different -y-chains designated G y and A-y, which contam either glycine (G7) or alanine (Arny) at position 1 36.12 The synthesis of the two types of chains is coded by two nonallelic structural gene complexes with the linkage arrangement t,t4 2, e, G’y, A”y, t,l’fll, b, fl. The ratio of G’y:A’y synthesized at birth is approximately 7:3 and declines during the first 6 mo of life. In certain hematologic disorders such as leukemia, aplastic anemia, childhood erythroblastopenia, and juvenile chronic granulocytic leukemia, as well as in in vitro culture systems, a reactivation of fetal hemoglobin synthesis occurs. A transient manifestation of fetal erythropoiesis also has been documented in a small number of patients recovering from bone marrow transplantation (BMT) that had been performed as a treatment for aplastic anemia and acute leukemia.7 We have undertaken a study to analyze the following aspects: ( 1 ) Is a repeated ontogeny a constant factor of erythropoiesis after BMT? (2) Do factors of donor or host influence the pattern of recovery?