Sign up for Table of Contents Alerts.

Email this page

Print this page

Perspectives

Leukemia and hematopoietic stem cells: Balancing proliferation and quiescence

Craig D. Jude, Justin J. Gaudet, Nancy A. Speck and Patricia Ernst

Purchase article for $19

Subscribe to this journal for $129/year

Chromosomal translocations that disrupt transcriptional regulators are frequently involved in the etiology of leukemia. To gain an understanding of the normal and pathologic roles of these transcriptional regulators, both gain- and loss-of-function mutations have been examined in the context of steady-state hematopoiesis. These studies have identified a remarkable number of genes whose loss-of-function phenotype includes a perturbation of hematopoietic stem cell (HSC) proliferation. As more of these models are generated and analyzed using commonly available tools, the regulatory pathways that control HSC quiescence and proliferation are becoming clearer. An emerging theme is that leukemia-associated transcriptional regulators coordinate the balance of proliferation and quiescence within the HSC pool by modulating the number and frequency of cells transiting the cell cycle. Uncoupling proliferation from differentiation by the aberrant generation of chimeric oncogenes that retain some, but not all of the attributes of the original transcription factor is likely to be an important step during leukemogenesis.

Authors

Craig D. Jude

Dartmouth Medical School; Hanover, NH

Justin J. Gaudet

Dartmouth Medical School; Hanover, NH

Nancy A. Speck

Dartmouth Medical School; Hanover, NH

Patricia Ernst

Dartmouth Medical School; Hanover, NH

Purchase article for $19

Subscribe to this journal for $129/year