The detection of normal hidden stem cells during the development of leukemia: assays with PGK isozyme

We evaluated the changes in the number of normal spleen colony-forming units (CFU-S) in the spleen and the bone marrow of C3H/He mice during the development of leukemia following the injection of the murine leukemia cell line, MK-8057, MK-8057 cells, originating in C3H/He PGK-1b mice, were injected into syngeneic C3H/He PGK-1a mice so that phosphoglycerate kinase (PGK) isozymes could be used to distinguish leukemic spleen colonies from normal colonies when cells from the spleen or bone marrow of the recipients were reinjected into lethally irradiated mice. Leukemic cells showed a logarithmic increase in the recipient mice and had replaced the bone marrow and the spleen completely by days 6-8; the mice started to die of leukemia after day 11. However, colonies examined from normal stem cells still comprised 60% of the total number of spleen colonies on day 6, 45% on day 8, and 20% on day 10. Furthermore, when the numbers of normal CFU-S were calculated as numbers per spleen, we found that they increased exponentially to a level 100 times higher than the normal level 10 days after injection of MK-8057 cells.