title: Comparison of megakaryopoiesis in vitro of paired peripheral blood progenitor cells and bone marrow harvested during remission in patients with acute myeloid leukaemia.
abstract: We have studied paired peripheral blood progenitor cells (PBPC) and bone marrow (BM) samples from 12 acute myeloid leukaemia (AML) patients following intensive chemotherapy, and assessed direct granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), megakaryocyte CFU (CFU-Mk) numbers and the production of CD61+ (platelet glycoprotein IIIa) cells in suspension culture in response to various haemopoietic growth factor combinations. We found that CFU-GM and BFU-E numbers per 105 mononuclear cells were similar in both AML PBPC and BM harvests; CFU-Mk numbers, however, were significantly higher in PBPC than BM. In addition, the higher total white cell count of the PBPC harvests meant that PBPC have much higher numbers of total progenitors per collection. CD61+ cell numbers in suspension cultures of AML PBPC and BM were lower than those of harvested normal marrow. However, response to pegylated recombinant human megakaryocyte growth and development factor (PEGrHuMGDF) both alone and in combination with other growth factors was qualitatively similar to that of normal BM. As with normal BM, response to PEGrHuMGDF alone did not increase further with addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin 6 (IL-6) or erythropoietin (EPO) in the AML PBPC and BM. Further responses over PEGrHuMGDF alone were seen when added with stem cell factor (SCF) or with a combination of SCF + IL-3 + EPO in both AML PBPC and BM cultures; however, the magnitude of the response was greater in the PBPC cultures. Response to PEGrHuMGDF + IL-3 was seen in the PBPC cultures but not in the AML BM. These data suggest that, in AML patients, there are proportionally more megakaryocyte progenitor cells in the mobilized PBPC than in the BM harvests, which would explain the more rapid platelet recovery following PBPC autografts.
authors.affiliation: University Department of Haematology, Manchester Royal Infirmary, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Briggs
authors.forename: J A
authors.initials: JA
authors.lastname: Adams
authors.forename: M L
authors.initials: ML
authors.lastname: Brereton
authors.forename: R
authors.initials: R
authors.lastname: Burgess
authors.forename: K
authors.initials: K
authors.lastname: Hyde
authors.forename: H
authors.initials: H
authors.lastname: Lenehan
authors.forename: J A
authors.initials: JA
authors.lastname: Yin
mesh_terms: D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD; D001792:Blood Platelets; D001854:Bone Marrow Cells / Q000166:cytology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology; D004921:Erythropoietin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis; D006801:Humans; D039661:Integrin beta3; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000097:blood*; D008264:Macrophages / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology* / Q000276:immunology; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins; D011092:Polyethylene Glycols / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology*; D013926:Thrombopoietin / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D006133:Growth Substances; D039661:Integrin beta3; D007377:Interleukin-3; D015850:Interleukin-6; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin