Stem cells in differentiation and neoplasia.

The stem cell concept continues to be very useful both for studies on cellular differentiation and for studies on neoplasia. At present the concept is being enlarged to include consideration of a new aspect: stem cell genetics, at the molecular level. Some questions are still to be answered. What is the basis for genetic regulation of "commitment," that is, the transition from pluripotent stem cells to committed progenitor cells? Does neoplasia involve changes in the genetic material of hemopoietic stem cell? To illustrate the ways in which genetic approaches may be used to provide new answers to these important questions, a minimal model of commitment at the molecular level is presented. The model is based on the assumption that movable genetic elements may play a hitherto-unsuspected role in the early stages of stem cell differentiation. It provides a simple explanation for the apparent close association between loss of potential for stem cell renewal and commitment. The possibility that analogous movable genetic elements may be involved in both the development of neoplastic cells and the differentiation of normal cells is also discussed. The need for caution in interpreting evidence for apparent differences in the genetic material of normal and neoplastic cells is stressed.