Stem cell renewal and differentiation in acute myeloblastic leukaemia.
The defining properties of stem cells are capacities for self-renewal and, after determination, a limited number of terminal divisions. The blast cells of acute myeloblastic leukaemia (AML) are maintained by stem cells with these two properties. Since renewal and differentiation can be assessed separately in cultures of AML blasts, these cancer cells provide a useful model for examining stem regulation; such studies have practical importance for future developments in the treatment of AML. This paper considers three aspects of blast cell biology. First, evidence is presented that self-renewal and differentiation are regulated by specific genes; further, the DNA encoding these genes has structural features that affect the chemosensitivity of self-renewal. This sensitivity varies from patient-to-patient and is an important attribute contributing to variation in treatment efficacy. Second, the effects of myelopoietic growth factors on blast stem cells are presented and discussed, as these bear on the regulation of the balance between renewal and differentiation. Finally, models of leukaemic haemopoiesis are considered in light of the experimental findings. The suggestion is advanced that leukaemia can be explained better by abnormalities of gene expression than by blocked differentiation.
McCulloch
E A
EA
Division of Biological Research, Ontario Cancer Institute, Toronto, Canada.
Minden
M D
MD
Miyauchi
J
J
Kelleher
C A
CA
Wang
C
C
D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*
D000970:Antineoplastic Agents; D006133:Growth Substances