Fetal antigens in human leukemia

Immunization of BALB/c male mice with human peripheral leukemic blasts effectively reduced the later formation of syngeneic fetal liver, but not bone marrow hematopoietic colonies in the spleen when these mice were lethally irradiated and challenged i.v. Fetal antigen was detected in 6 of 6 lymphocytic leukemic patients and in 4 or 8 myelocytic leukemia patients and was correlated with low cellular levels of sialic acid. A rabbit antiserum to BALB/c 15 day fetal liver cells labeled only 0 to 2% of normal donor peripheral leukocytes in indirect immunofluorescence but reached with 10 to 21% of leukemic peripheral blasts. Active disease bone marrow on the same patients gave 7 to 40% fluorescent cells. Two remission bone marrow samples were negative and 1 had 44% fluorescent cells. Using this antiserum coupled to sepharose, affinity column separation of KCl extracts from mouse and human fetal liver and from chronic lymphocytic leukemia has produced 4 common protein bands (identifiable on polyacrylamide gel electrophoresis). Sera from mice immunized with leukemic blasts reacted with syngeneic fetal liver cells, but not with bone marrow or adult liver by immunofluorescence. While only 3 to 10% of the cells were positive in the unfractionated fetal liver, separation of cells by density on discontinuous albumin gradients gave 15 to 40% fluorescence in the 23% albumin fraction. This represented a 70 to 90% purification of the leukemia cross reactive cell (recovery of fluorescent cells) and, concomitantly, 79% recovery of the hematopoietic stem cell, as determined by the spleen colony assay. The data suggest that antisera raised against the purified fetal hematopoietic stem cells or the solubilized cross reactive leukemia antigen may be valuable in monitoring the clinical status of leukemia patients.