Proliferative effects of a recombinant human granulocyte colony-stimulating factor (rG-CSF) on highly enriched hematopoietic progenitor cells.

Human multipotential and committed hematopoietic progenitor cells require the presence of specific glycoproteins, termed "colony-stimulating factors" (CSFs) for survival, clonal proliferation, and differentiation. Recently, a pluripotent G-CSF, constitutively produced by the human bladder carcinoma line 5637, has been purified to apparent homogeneity [11 and molecularly cloned with the complementary DNA copy of the gene expressed in Escherichia coli [2]. This factor induces terminal differentiation of the murine myelomonocytic cell line WEHI3B(D +), the human promyelocytic cell line HL60, and leukemic cells from patients with certain forms of ANLL [2, 3] and has been shown to stimulate the growth of day-7 granulocyte colonies, erythroid bursts (BFU-E), and multilineage colonies (CFUGEMM) from human bone marrow [1-31. Despite its similarity with murine G-CSF [41, the latter does not support the proliferation of BFU-E and CFU-GEMM [51, biological activities shared by murine IL3 and GMCSF [6-8]. However, IL3 has not been reported to induce differentiation of leukemic cells [9], no significant homology was found between the deduced amino acid sequence for hG-CSF and those for murine IL3 [10, 111 and murine and human GM-CSF [12, 13], and specific binding of radio labeled hGCSF was inhibited by an excess of unlabeled