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.
Basch
R S
RS
Department of Pathology, New York University Medical Center, NY, USA.
Zhang
X M
XM
Dolzhanskiy
A
A
Karpatkin
S
S
D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013926:Thrombopoietin / Q000494:pharmacology
D009363:Neoplasm Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D004247:DNA; D013926:Thrombopoietin