Some circulating factors which influence granulocyte-monocyte production in the chick with myeloblastic leukemia

Soft-agar cloning was used to investigate possible granulopoietic-monopoietic regulatory defects in the chick with myeloblastic leukemia induced by avian myeloblastosis virus. The plasma levels of granulocyte-monocyte colony-stimulating activity (CSA) of normal and leukemic plasmas were the same when undiluted or unfractionated plasmas were tested. However, dilution or fractionation revealed elevations in plasma CSA levels in the leukemic animals. Most of the activity in both normal and leukemic plasma eluted in the void-volume peak during Sephadex G-200 gel filtration, and the CSA levels in the leukemic peak were increased 5- to 10-fold. This increase did not reflect higher levels of an inhibitory lipoprotein eluting in the void volume since the differential between normal and leukemic plasma was present after delipidation. We therefore investigated the possibility that a nonlipoprotein inhibitor was present. Sephadex G-200 chromatography of leukemic plasma revealed that a potent inhibitor of colony formation was present in one of the peaks of material eluting from the column. Eight micrograms of this material inhibited colony formation by 50%. This inhibitory material was not detected in corresponding fractions obtained after chromatography of normal plasma. These data show that plasma from the chick with myeloblastic leukemia has marked elevated levels of CSA and that it also contains an inhibitor of colony formation which is absent or present at very low levels in normal plasma. Finally, leukemic plasma contained abundant amounts of avian myeloblastosis virus polypeptides which are being investigated for possible relationships to the above-described activities.