Expression of CD41 and c-mpl does not indicate commitment to the megakaryocyte lineage during haemopoietic development

Haemopoietic progenitors with the phenotype expected of early megakaryocyte precursors (CD34(+)CD41(+)) were isolated from normal human bone marrow or induced in culture from CD34(+)CD41(-) bone marrow cells by treatment with thrombopoietin (TPO) or IL-3, We found that although this population included the majority of cells that can form CFU-MK in culture, it also contained both erythroid and myeloid progenitors. The clonogenic potential of the CD34(+)CD41(+)-induced cells was greater than that of isolated CD34(+)CD41(+) cells in that the isolated cells only formed CFU-MK and BFU-e, whereas the induced cells formed myeloid colonies as well. Glycophorin was found on isolated CD34(+)CD41(+) cells, not on induced cells. Its presence distinguished between MK and erythroid progenitors. Separation of a CD34(+)CD41(+) glycophorin A(+) population resulted in the isolation of a highly purified population of BFU-e. A major portion of the cells that expressed CD34(+)CD41(+), in either cohort, were of the erythroid lineage. True MK progenitors were present in the CD34(+) population in greater proportion than in whole marrow and were further enriched amongst CD34(+) populations that expressed CD41. The presence of the thrombopoietin (TPO) receptor, c-mpl, did not correlate with inducibility of the gpIIbIIIa complex since essentially all CD34(+) progenitors, including the earliest identifiable human haemopoietic progenitors (CD34(+)CD38(-) cells), expressed c-mpl mRNA detectable by PCR regardless of their ultimate fate, Thus neither the expression of CD41 nor the expression of c-mpl was predictive of commitment to the MK lineage.