Acidic isoferritins (leukemia-associated inhibitory activity) fail to inhibit blast proliferation in acute myelogenous leukemia.
Cell-free extracts of bone marrow and blood cells from patients with leukemia contain an inhibitor of normal granulocyte/macrophage progenitor (CFU-GM) proliferation (leukemia-associated inhibitory activity, LIA) identified as acidic isoferritins. A comparison was made of the action of crude LIA prepared from frozen-thawed leukemic blood cells and purified spleen ferritin from a patient with chronic myelogenous leukemia, on the proliferation of blast progenitors from patients with acute myelogenous leukemia (AML), and on the promyelocytic leukemia cell line, HL-60. Crude LIA showed no inhibition of blast progenitor or HL-60 proliferation at low concentrations, but inhibited the proliferation of CFU-GM. At higher concentrations, crude LIA inhibited both blast cells and CFU-GM. Purified spleen ferritin failed to inhibit blast progenitors or HL-60 cells at any concentration tested, but inhibited both 70-day and 14-day CFU-GM. Using the thymidine "suicide" technique, the action of LIA was confirmed as being on CFU-GM in S-phase, but it failed to affect the proliferation of blast cell in S-phase. It is concluded that acidic isoferritins inhibit normal CFU-GM but not blast cells from patients with AML. Acidic isoferritins could confer a proliferative advantage of the leukemic clone over its normal counterparts.
D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005293:Ferritins / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D008264:Macrophages / Q000166:cytology
D003115:Colony-Stimulating Factors; C020391:acidic isoferritin; D005293:Ferritins