TOWARD A LEUKEMIA TREATMENT STRATEGY BASED ON THE PROBABILITY OF STEM-CELL DEATH - AN ESSAY IN HONOR OF DR. FREIREICH,EMIL,J

Dr. Emil J Freireich is a pioneer in the rational treatment of cancer in general and leukemia in particular, This essay in his honor suggest s that the cell kill concept of chemotherapy of acute myeloblastic leu kemia be extended to include two additional ideas, The first concept i s that leukemic blasts, like normal hemopoietic cells, are organized i n hierarchies, headed by stem cells, In both normal and leukemic hemop oiesis, killing stem cells will destroy the system; furthermore, both normal and leukemic cells respond to regulators. It follows that acute myelogenous leukemia should be considered as a dependent neoplasm, Th e second concept is that cell/drug interaction should be considered as two phases, The first, or proximal phase, consists of the events that lead up to injury; the second, or distal phase, comprises the respons es of the cell that contribute to either progression to apoptosis or r ecovery, Distal responses are described briefly, Regulated drug sensit ivity is presented as an example of how distal responses might be used to improve treatment.