Department of Clinical Physiology University of Ulm D 79 Ulm (Donau) Germany

1. Introduction

At the request of the organizers of this workshop on "Modern Trends in Human Leukemia II" we have been asked to review briefly some aspects of the physiology and pathophysiology of myelopoiesis, focusing mainly on the problems of the obvious deficiency of this system in case of acute myelocytic leukemia to provide an adequate number of granulocytes. A vast amount of information has been collected during the last lor 2 decades on the possibilities and limitations of cell production and differentiation in normal and leukemic myelopoieses. In spite of this, we have to confess today that there are many more open questions than solved problems. It probably is correct to state that "we are still quite ignorant about normal and leukemic cell production and differentiation but at a higher level" than 17 years ago, when the first cell kinetic study utilizing tritiated thymidine as a specific DNA label was performed in Dr. Cronkite's laboratory (1,2,3).

It is therefore the purpose of this presentation to outline the present concept of normal and leukemic cell proliferation and differentiation using granulocyte kinetics as a model. This will lead to the conclusion that the obvious deficiency of granulocyte production in acute leukemia is a consequence of a highly ineffective cell proliferation and differentiation in the appropriate precursor compartments and points to the stem-cell pool as the major site of leukemic cell transformation.