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 tr eated 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 cumulat ive numbers. Similarly, a 12-fold increase in the numbers of megakaryo cytes (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 megakaryoc ytopoiesis in patients with AML in first remission, restoring the Meg- CFC compartment to normal values, a result with potential clinical imp lications for their treatment with autologous transplantation.