title: Recombinant human megakaryocyte growth and development factor (MGDF) increases the numbers of megakaryocyte progenitor cells to normal values in long-term bone marrow cultures of patients with AML in first remission.
abstract: The megakaryopoietic potential in the bone marrow (BM) of patients in first remission after treatment for acute myelogenous leukaemia (AML) was investigated using long-term bone marrow cultures (LTC) stimulated with megakaryocyte growth and development factor (MGDF). The baseline number of megakaryocyte colony-forming cells (Meg-CFC) was very low. However, there was a 10 to 100-fold increase of Meg-CFC in cultures treated with 10 ng/ml MGDF with mean numbers within the normal range for the first 4 weeks of culture with a 24-fold increase in their cumulative numbers. Similarly, a 12-fold increase in the numbers of megakaryocytes (MKs) was found by CD61 immunostaining. These effects were lost at the dose of 100 ng/ml. In contrast, the cumulative mean numbers of Meg-CFC in the control cultures from normal bone marrow (NBM) were not significantly different from those in cultures treated with 10 or 100 ng/ml MGDF. These results demonstrate that MGDF stimulates megakaryocytopoiesis in patients with AML in first remission, restoring the Meg-CFC compartment to normal values, a result with potential clinical implications for their treatment with autologous transplantation.
authors.affiliation: Cancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
authors.forename: C
authors.initials: C
authors.lastname: Kasper
authors.forename: A
authors.initials: A
authors.lastname: Schwarzer
authors.forename: E A
authors.initials: EA
authors.lastname: De Wynter
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: T M
authors.initials: TM
authors.lastname: Dexter
authors.forename: D
authors.initials: D
authors.lastname: Ryder
authors.forename: N G
authors.initials: NG
authors.lastname: Testa
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects*; D002452:Cell Count; D046508:Culture Techniques; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects*; D008875:Middle Aged; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human