Stromal Function in Long Term Bone Marrow Culture of Patients with Acute Myeloid Leukemia
Inhibition of normal hemopoiesis-peripheral blood pancytopenia and complete absence of normal colony forming cells in bone marrow [3, 4], is a regular finding in acute (AML) myeloid leukemias . However, this inhibition is reversible. Polyclonal normal hemopoiesis is reestablished in more than two thirds of cases of AML during complete remission, demonstrating the existence of normal stem cells . A few pathogenic mechanisms have been proposed to account for this process: cell crowding, synthesis by leukemic cells of inhibitor substances, cell contact processes and deficiency in the stromal cell microenvironment . Several humoral inhibitors were found to be produced by leukemic cells such as acidic isoferritins, LAI and TNF-alpha [4, 5, 6]. Very little is known about the role of the microenvironment in the inhibition of normal hemopoiesis.
KeywordsAcute Myeloid Leukemia Bone Marrow Cell Normal Hemopoiesis Normal Bone Marrow Cell Long Term Bone Marrow Culture
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- 3.Bernstein, I.D., Singer, J.W., Smith, F.O., Andrews, R.G., Flowers, D.A., Petersens, J., Steinman, L., Najfeld, V., Savage, D., Frauchtman, S., Arlin, Z., Fialkow, P.J. (1992) Differences in the frequency of normal and clonal precursors of colony forming cells in chronic myelogenous leukemia and acute myelogenous leukemia. Blood, 79, 1811–1816.PubMedGoogle Scholar
- 9.Rice, A., Reiffers, J., Bernard, Foure, E., Bascans, E., Lacombe, F., Marit, G., Broustet, A. Incomplete stroma formation after allogeneic marrow or autologous blood stem cell transplantation. Nouv. Rev. Fr. Hematol, 34, 167–174.Google Scholar
- 10.Mayani, H., Guilbert, L.J., Clark, J.C., Belch, A.R., Janowska-Wieczorek, A. (1992) Composition and functional integrity of the in vitro hemopoietic microenvironment in acute myelogenous leukemia: Effect of macrophage colony-stimulating factor. Experimental Hematology, 20, 1077–1084.PubMedGoogle Scholar
- 11.Cashman, J.D., Eaves A.C., Raines, E.W., Ross, R., Eaves, C.J., (1990) Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long term human marrow cultures. I. Stimulatory role of a variety of mesenchymal cell activators and inhibitory role of TGF-beta. Blood 75: 96–101.PubMedGoogle Scholar
- 13.Eaves, C.J., Cashman, J.D., Kay, R.D., Dougherty, C.J., Otsuka, T., Gaboury, L.A., Hogge, D.E., Lansdorp, P.M., Eaves, A.C., Humphries, R.K. (1991) Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer. Blood, 78, 110–117.PubMedGoogle Scholar
- 14.Delforge, A., Lagneaux, L., Dorval, C, Bron, D., Bosmans, E., Stryckmans, P. (1993) Excessive production of TGF-beta by bone marrow stromal cells in B-cell chronic lymphocytic leukemia (B- CLLo inhibits growth of hematopoietic precursors and IL-6 production. Experimental Hematology, 21, 1090 (abstr).Google Scholar
- 16.Lichtman, M.A., (1984) The relationship of stromal cells to hemopoietic cells in marrow. In: Long term bone marrow cultures, edited by D.G. Wright and J.S. Greenberg, pp. 3–29. New York: Alan R. Liss.Google Scholar