JunB protects against myeloid malignancies by limiting hematopoietic stem cell proliferation and differentiation without affecting self-renewal.

Journal: 
Cancer Cell
Publication Year: 
2009
Authors: 
Marianne Santaguida , Koen Schepers , Bryan King , Amit J Sabnis , E Camilla Forsberg , Joanne L Attema , Benjamin S Braun , Emmanuelle Passegue
Public Summary: 
Research article investigating the mechanisms by which the transcription factor JunB prevents leukemic transformation of blood stem cells.
Scientific Abstract: 
Loss of the JunB/AP-1 transcription factor induces a myeloproliferative disease (MPD) arising from the hematopoietic stem cell (HSC) compartment. Here, we show that junB inactivation deregulates the cell-cycle machinery and increases the proliferation of long-term repopulating HSCs (LT-HSCs) without impairing their self-renewal or regenerative potential in vivo. We found that JunB loss destabilizes a complex network of genes and pathways that normally limit myeloid differentiation, leading to impaired responsiveness to both Notch and TGF-beta signaling due in part to transcriptional deregulation of the Hes1 gene. These results demonstrate that LT-HSC proliferation and differentiation are uncoupled from self-renewal and establish some of the mechanisms by which JunB normally limits the production of myeloid progenitors, hence preventing initiation of myeloid malignancies.

© 2013 California Institute for Regenerative Medicine