BCL2 oncogene protein expression in human hematopoietic precursors during fetal life.

ABSTRACT

BCL2 proto-oncogene encodes a 25-kD protein that is characteristically localized in the inner mitochondrial membrane of the cell. It has been reported that BCL2 protein has the unique functional role of blocking programmed cells death without affecting proliferation. We have analyzed the expression of the BCL2 protein in fetal hematopoietic tissues from the 10th week of gestational age onward. Fetal thymus, liver, and bone marrow and cord blood were investigated. The experiments were performed by the alkaline-antialkaline phosphatase (APAAP) technique by staining air-dried acetone-fixed cytospins and by dual-color immunofluorescent assay by staining mononuclear cell suspensions with monoclonal antibodies detecting BCL2 protein and antigens expressed by different hematopoietic subsets. Flow cytometric analyses were performed on FACSort's Comsort 32 (Becton Dickinson, San Jose, CA). The results have shown that the BCL2 protein is expressed in human fetal ontogenesis at the earliest stages examined. The major conceptual aspects of the results are 1) BCL2 is largely expressed in the hematopoietic cells during ontogenesis. BCL2+ cells include both immature and more differentiated subsets. Moreover, the 25-kD protein is expression in cell subsets well known to be high proliferating. This behavior suggests that BCL2 could have more complex functions than those previously described. 2) The expression in the major part of CD34+ cells suggests that BCL2 could play a role in stem cell survival. 3) BCL2 is expressed in not only medullary but also cortical thymocytes, where it could cooperate in positive selection processes. 4) The involvement of BCL2 in the immunosurveillance is indicated not only by its role in B and T cell lineages but also by its expression in particular subsets like that of the cytoplasmic CD3+ fetal liver NK cells. 5) The discrepancy observed between the results of transgenic mice analysis and in vitro inhibition experiments by antisense oligonucleotides performed for understanding BCL2 functions must stress the importance of the direct immunologic analysis of BCL2 in human hematopoietic cells.