REVIEW ARTICLE Transcription Factors, Normal Myeloid Development, and Leukemia

cells specifically? (5) How does a common progenitor cellT become one type (myeloid) rather than another?RANSCRIPTION FACTORS play a major role in dif-ferentiation in a number of cell types, including the Currently, models have been advanced proposing that he-various hematopoietic lineages.1-4 In the hematopoietic sys-matopoietic lineage determination is driven extrinsicallytem, stem cells undergo a process of commitment to multipo-(through growth factors, stroma, or other external influ-tential progenitors, which in turn give rise to mature blood ences),20,21 intrinsically (as described in stochastic models),22cells. Although a number of transcription factors have been or both.23 Our working hypothesis is that, regardless ofidentified that play a role in the development of erythroid whether the environmental or stochastic models are invoked,or lymphoid lineages,5-9 only in the past few years have those transcription factors are the final common pathway drivingfactors that influence development of myeloid cells been differentiation and that hematopoietic commitment to differ-identified and studied. In particular, recent studies of the ent lineages is driven by alternative expression of specificregulation of normal myeloid genes, as well as the study of combinations of transcription factors, which often induceleukemias, have suggested that transcription factors play a expression of growth factor receptors or growth factors. Themajor role in both myeloid differentiation and leukemogene-transcription factors are often activated in positive autoregu-sis.10-12a To understand the process of normal myeloid differ-latory loops, helping to explain the irreversible differentia-entiation, it is important to identify and characterize the tran-tion process found in human hematopoiesis. Experimentalscription factors that specifically activate important genes i