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.
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.
Kasper
C
C
Cancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
Schwarzer
A
A
De Wynter
E A
EA
Chang
J
J
Dexter
T M
TM
Ryder
D
D
Testa
N G
NG
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
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human