Abstract
Reentry of small leukemic blast cells into a proliferative phase was demonstrated in a 3 yr old girl with untreated acute lymphoblastic leukemia. Since the proliferating leukemic cell compartment in this disease is not self-maintaining, continual entry of cells into this compartment is necessary to prevent depletion of proliferating cells. In order to identify the source of replacement cells, the rate of change of tritiated thymidine-labeled cells in the proliferating compartment was observed by means of serial bone marrow samples under two conditions. In the first study period only 10% of small leukemic blast cells were labeled, and in the second study period 72% of this population had become lebeled. During the first period the proliferating blast cells were rapidly replaced by unlabeled cells, while during the second period the replacement cells were coming largely from a labeled cell source. The only identifiable source of cells for maintenance of the proliferating population which was virtually unlabeled during the first period and largely labeled during the second period was the population of small leukemic blast cells.
The finding that the small blast cells are only temporarily nonproliferative could account for effectiveness of therapy directed primarily against a dividing cell population. Persistence of some cells with longer resting times into remission could provide a focus for subsequent relapse.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BASERGA R., GOLD R. THE UPTAKE OF TRITIATED THYMIDINE BY NEWLY TRANSPLANTED EHRLICH ASCITES TUMOR CELLS. Exp Cell Res. 1963 Sep;31:576–585. doi: 10.1016/0014-4827(63)90404-x. [DOI] [PubMed] [Google Scholar]
- Chan B. W., Hayhoe F. G., Bullimore J. A. Effect of extra-corporeal irradiation of the blood on bone marrow activity in acute leukaemia. Nature. 1969 Mar 8;221(5184):972–974. doi: 10.1038/221972a0. [DOI] [PubMed] [Google Scholar]
- Donachie W. D. Relationship between cell size and time of initiation of DNA replication. Nature. 1968 Sep 7;219(5158):1077–1079. doi: 10.1038/2191077a0. [DOI] [PubMed] [Google Scholar]
- Gavosto F., Pileri A., Gabutti V., Masera P. Cell population kinetics in human acute leukaemia. Eur J Cancer. 1967 Nov;3(4):301–307. doi: 10.1016/0014-2964(67)90011-4. [DOI] [PubMed] [Google Scholar]
- Gavosto F., Pileri A., Gabutti V., Masera P. Non-self-maintaining kinetics of proliferating blasts in human acute leukaemia. Nature. 1967 Oct 14;216(5111):188–189. doi: 10.1038/216188a0. [DOI] [PubMed] [Google Scholar]
- Harding C. V., Wilson W. L., Wilson J. R., Reddan J. R., Reddy V. N. Triggering of the cell cycle of an organized tissue in vitro. J Cell Physiol. 1968 Dec;72(3):213–220. doi: 10.1002/jcp.1040720308. [DOI] [PubMed] [Google Scholar]
- Mathé G., Schwarzenberg L., Mery A. M., Cattan A., Schneider M., Amiel J. L., Schlumberger J. R., Poisson J., Wajcner G. Extensive histological and cytological survey of patients with acute leukaemia in "complete remission". Br Med J. 1966 Mar 12;1(5488):640–642. doi: 10.1136/bmj.1.5488.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mauer A. M., Fisher V. Characteristics of cell proliferation in four patients with untreated acute leukemia. Blood. 1966 Sep;28(3):428–445. [PubMed] [Google Scholar]
- NIES B. A., BODEY G. P., THOMAS L. B., BRECHER G., FREIREICH E. J. THE PERSISTENCE OF EXTRAMEDULLARY LEUKEMIC INFILTRATES DURING BONE MARROW REMISSION OF ACUTE LEUKEMIA. Blood. 1965 Aug;26:133–141. [PubMed] [Google Scholar]
- PELC S. R. The stripping-film technique of autoradiography. Int J Appl Radiat Isot. 1956 Nov;1(3):172–177. doi: 10.1016/0020-708x(56)90003-5. [DOI] [PubMed] [Google Scholar]
- ROBINSON S. H., BRECHER G. DELAYED INCORPORATION OF TRITIATED THYMIDINE INTO DNA. Science. 1963 Oct 18;142(3590):392–393. doi: 10.1126/science.142.3590.392. [DOI] [PubMed] [Google Scholar]
- ROBINSON S. H., BRECHER G., LOURIE I. S., HALEY J. E. LEUKOCYTE LABELING IN RATS DURING AND AFTER CONTINUOUS INFUSION OF TRITIATED THYMIDINE: IMPLICATIONS FOR LYMPHOCYTE LONGEVITY AND DNA REUTILIZATION. Blood. 1965 Sep;26:281–295. [PubMed] [Google Scholar]
- Saunders E. F., Lampkin B. C., Mauer A. M. Variation of proliferative activity in leukemic cell populations of patients with acute leukemia. J Clin Invest. 1967 Aug;46(8):1356–1363. doi: 10.1172/JCI105628. [DOI] [PMC free article] [PubMed] [Google Scholar]