BCL2 ONCOGENE PROTEIN EXPRESSION IN HUMAN HEMATOPOIETIC PRECURSORS DURING FETAL LIFE

BCL2 proto-oncogene encodes a 25-kD protein that is characteristically localized in the inner mitochondrial membrane of the cell. It has bee n reported that BCL2 protein has the unique functional role of blockin g programmed cell death without affecting proliferation. We have analy zed 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 pe rformed by the alkaline-antialkaline phosphatase (APAAP) technique by staining air-dried acetone-fixed cytospins and by dual-color immunoflu orescent assay by staining mononuclear cell suspensions with monoclona l antibodies detecting BCL2 protein and antigens expressed by differen t hematopoietic subsets. Flow cytometric analyses were performed on FA CSort's Consort 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 res ults are 1) BCL2 is largely expressed in the hematopoietic cells durin g ontogenesis. BCL2(+) cells include both immature and more differenti ated subsets. Moreover, the 25-kD protein is expressed 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 o nly medullary but also cortical thymocytes, where it could cooperate i n positive selection processes. 4) The involvement of BCL2 in the immu nosurveillance is indicated not only by its role in B and T cell linea ges but also by its expression in particular subsets like that of the cytoplasmic CD3(+) fetal liver NK cells. 5) The discrepancy observed b etween 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 a nalysis of BCL2 in human hematopoietic cells.