Leukemia and Hematopoietic Stem Cells: Balancing Proliferation and Quiescence

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2008 Feb 2

PMID 18239455

Citations 27

Authors

Craig D Jude

Justin J Gaudet

Nancy A Speck

Patricia Ernst

Affiliations

Soon will be listed here.

Abstract

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.

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