Suppression of normal granulopoiesis in vitro by a leukemia-associated inhibitor (LAI) of acute and chronic leukemia

To determine if normal granulopoiesis can be suppressed by substances produced by cells from patients with leukemia. conditioned media from such cells were assayed for their ability to reduce the fraction of normal CFU-c in S-phase or inhibit cluster/colony formation in agar cultures. Low-density (<1 .077 g/ml) marrow or blood cells from patients with leukemia. but not from normals. were shown to release a high molecular weight substance (>300.000 daltons) called "leukemia-associated inhibitor" (LAl) that reduces the fraction of normal marrow CFU-c in S-phase. This effect appeared to be reversible. In 10/12 patients with CML, 12/15 with AMI, 1 /7 with CLI. and 2/6 with ALL. significant amounts of LAI were detected. LAI also reduces the labeling index of normal myeloblasts. LAI is resistant to heating to 6O C for 10 mm.