Considerations on the possible origins of fetal hemoglobin cells produced in developing tumors

Although tumor angiogenesis in relation to cancer therapy has been widely investigated for more than four decades, its counterpart tumor hematopoiesis has not been equally considered. In that respect, in our long-term immunohistochemical examination of fetal hemoglobin (HbF) cells in various solid tumors, we have observed signs of fetal hematopoiesis in situ within the tumors. We hypothesize that this observed fetal hematopoiesis, involving angiogenesis, mirrors mammalian blood system development in the embryo and the fetus; this is consistent with the concept of the hemogenic endothelial progenitor, common to endothelial and hemopoietic cells. Based on this assumption, there should exist in tumors at least two routes of hematoangiogenesis: one of fetal (HbF) hematopoiesis and the other of adult (HbA) hematopoiesis, each one deserving a different therapeutic approach. In the fetal route, HbF should support tumor growth by virtue of its high oxygen affinity.