Differentiation of human acute myeloid leukaemia cells in response to exogenous and endogenous stimuli: Different patterns of response suggested by a bioassay system

Abstract

The object of this study was to devise quantitative bioassay systems suitable for the analysis of differentiation in acute myeloid leukaemia (AML) in response to both endogenous (bone marrow) and exogenous stimuli. Dose response analyses of the relationship between exogenous differentiation stimulus (supplied by peripheral blood mononuclear leucocytes) and clone cell maturity in double layer semi-solid agar cultures, were used to identify a measure of response with a linear relationship to differentiation stimulus on which bioassay systems could be based. All 7 AML samples tested at presentation and 1 sample from a patient during the regenerative phase after therapy, exhibited some response to exogenous differentiation stimulus. Only in the latter was there no significant difference in the response of test and reference cells. The other 7 showed marked variation in the pattern of the response in vitro. There was no close correlation between differentiation capacity in vitro and extent of differentiation observed in vivo. This discrepancy might be related to varying availability of endogenous differentiation stimulus in different patients. The technique for assaying differentiation response was adapted to demonstrate and quantify the endogenous differentiation stimulus (the stimulus provided by the leukaemic patient's marrow cells). The results suggest that in some patients the level of this stimulus may be a major determinant in the level of differentiation achieved in vivo.