Stabilization of Labile Glucocorticoid-Receptor Complexes from Acute Nonlymphocytic Leukemia Cells by a Factor from Chronic Lymphocytic Leukemia Cells
AbstractGlucocorticoid-receptor complexes in cytoplasm from normal lymphoid and leukemia cells incubated with glucocorticoid can be resolved into three different components, activated, nonactivated, and mero-receptor complexes, in relative amounts, dependent on the conditions to which the cells or cytosols are exposed. Recently, we reported that cytosols of acute nonlymphocytic leukemia (ANLL) cells contained high levels of meroreceptor complexes relative to those of chronic lymphocytic leukemia (CLL) or normal lymphoid cells. In the present study, we examined the cause for the lability of cytosolic complexes of ANLL cells. Mero-receptor accumulated rapidly in ANLL cytosols in a time-dependent fashion. The accumulation was most rapid in cytosols which contained activated receptor complexes, but it also occurred in cytosols containing only nonactivated receptor forms. Molybdate (20 m M ) slowed but did not prevent the conversion to mero-receptor. Cytosols of ANLL specimens of the M 4 French-American-British class (with monocytoid differentiation properties), in general, contained more stable complexes than did specimens of the M 1 to M 3 French-American-British classes (primarily myelocytic differentiation) suggesting that lability may in part be related to the state or direction of differentiation of the leukemic cells. In keeping with this hypothesis, cytosols of polymorphonuclear cells isolated from normal blood were much more labile than were those of monocytes. Mixing experiments with ANLL and CLL cells showed that the lability of ANLL complexes is not due simply to a higher content of proteolytic enzymes in these cells, because addition of ANLL cells or cytosols to CLL specimens did not result in increased mero-receptor. To the contrary, addition of CLL cells to ANLL specimens greatly stabilized the cytosolic complexes. These findings indicate the presence of an endogenous factor, present in CLL but lacking in ANLL cells, which is capable of stabilizing cytosolic complexes. 1 This work was supported in part by American Cancer Society Grant CA-167, USPHS Grants CA-26273, CA-17323, AM-03535, the core grant (CA-23108) of the Norris Cotton Cancer Center, and the Coleman Leukemia Research Fund. 2 Supported during part of these studies by National Research Service Award CA-09367 and supported currently by a Fellowship Award from the Leukemia Society of America. Current address: National Cancer Institute, Laboratory of Pathology, Bldg. 10, Room 2N-113, Bethesda, Md. 20205. 3 To whom requests for reprints should be addressed.