The expression of Bcl-x is downregulated during differentiation of human hematopoietic progenitor cells along the granulocyte but not the monocyte/macrophage lineage

Expression of the apoptosis inhibitory protein Bcl-x was studied in CD34(+) hematopoietic precursor cells and in the promyelocytic leukemia cell line HL-60. The enriched population of CD34(+) cells (more than 95%) was cultured in the presence of stem cell factor, interleukin-3 (IL-3), IL-6, and either granulocyte colony-stimulating factor or macrophage colony-stimulating factor to achieve granulocyte or monocyte/macrophage differentiation, respectively. The expression of Bcl-x increased in the early stages of both differentiation pathways, However, by day 21 of culture mature granulocytes were Bcl-x-negative, whereas monocytes/ macrophages either maintained or increased the expression of Bcl-x. The pattern of Bcl-x expression in the differentiated CD34(+) cells was similar to that observed in HL-60 cells differentiated along the granulocyte lineage (induced by incubation with retinoic acid), or along the monocyte/macrophage lineage (induced by incubation with phorbol diester), The bcl-x transcript predominant in HL-60 and CD34(+) cells differentiated into monocytes/macrophages was bcl-x(L). Although little is yet known regarding the functional significance of Bcl-x within the granulomonocytic compartment, marked changes in the pattern of its expression, as observed during granulomonocytic differentiation of HL-60 and CD34(+) cells, are likely to alter the life span of mature granulocytes and monocytes/macrophages. (C) 1997 by The American Society of Hematology.