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. 2013 May 15;11(1):33.
doi: 10.1186/1478-811X-11-33.

Targeting self-renewal pathways in myeloid malignancies

William A Sands  1 , Mhairi Copland, Helen Wheadon
Affiliations

Targeting self-renewal pathways in myeloid malignancies

William A Sands et al. Cell Commun Signal. .

Abstract

A fundamental property of hematopoietic stem cells (HSCs) is the ability to self-renew. This is a complex process involving multiple signal transduction cascades which control the fine balance between self-renewal and differentiation through transcriptional networks. Key activators/regulators of self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behaviour. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. Here we will focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies.

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Figures

Figure 1
Figure 1
Cross-talk between self-renewal pathways involved in myeloid malignancies.
See this image and copyright information in PMC

References

    1. Il-Hoan O. Microenvironmental targeting of Wnt/β-catenin signals for hematopoietic stem cell regulation. Exp Opin Biol Thera. 2010;10:1315–1329. doi: 10.1517/14712598.2010.504705. - DOI - PubMed
    1. Coskun S, Hirschi KK. Establishment and regulation of the HSC niche: roles of osteoblastic and vascular compartments. Birth Defects Res. 2010;90:229–242. doi: 10.1002/bdrc.20194. - DOI - PMC - PubMed
    1. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–1121. doi: 10.1016/j.cell.2005.05.026. - DOI - PubMed
    1. Goardon N, Marchi E, Atzberger A, Quek L, Schuh A, Soneji S, Woll P, Mead A, Alford KA, Rout R, Chaudhury S, Gilkes A, Knapper S, Beldjord K, Begum S, Rose S, Geddes N, Griffiths M, Standen G, Sternberg A, Cavenagh J, Hunter H, Bowen D, Killick S, Robinson L, Price A, Macintyre E, Virgo P, Burnett A, Craddock C. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell. 2011;19:138–152. doi: 10.1016/j.ccr.2010.12.012. - DOI - PubMed
    1. Cozzio A, Passegué E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev. 2003;17:3029–3305. doi: 10.1101/gad.1143403. - DOI - PMC - PubMed

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