TRANSFORMING GROWTH FACTOR-BETA INHIBITS THE PROLIFERATION OF THE BLAST CELLS OF ACUTE MYELOBLASTIC-LEUKEMIA

  • 1 July 1988
    • journal article
    • research article
    • Vol. 72  (1) , 159-164
Abstract
The effect of transforming growth factor .beta. (TGF.beta.) on proliferation and differentiation of peripheral blast precursors in acute myeloblastic leukemia (AML) was investigated. TGF.beta. induced a dose-dependent inhibition of blast clonogenic cells in suspension and methylcellulose cultures in the presence of optimal concentrations of stimulators provided by conditioned media from the bladder cell line HTB9 (HTB9-CM) or the recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). On removal of TGF.beta., blast clonogenic cell proliferation recovers to the same level as that observed in control cultures, indicating that the effect is reversible. There was no induction of cell differentiation, as indicated by morphological and functional studies (production of superoxyde anions). Cell cycle analysis by thymidine uptake and flow cytometry with a DNA binding dye indicated that TGF.beta. caused a delay in progression into S and G2/M phases of the cell cycle without affecting cell viability. Thus, TGF.beta. appears to have a cytostatic rather than cytolytic effect on blast precursors and might therefore play a role as a negative regulator in hematopoiesis.