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Bone Marrow Transplant -- Introduction and Basics


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#21 warrior

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Posted 28 April 2011 - 04:48 AM

There is the problem of identifying the Leukeic sem cells from healthy sc and then there is the problem of getting the stem cells to leave their niche in  the bone marrow. CML is the model for studying this problem as when the tyrosine kinase inhibitor is removed the disease returns. Here is a nice review article on approachs to getting those lcs to leave their home.

Perspectives

Nature Reviews Immunology 10, 201-209 (March 2010) | doi:10.1038/nri2726

Opinion: Awakening dormant haematopoietic stem cells

Andreas Trumpp1,                Marieke Essers &                Anne Wilson

Abstract

Haematopoietic  stem cells (HSCs) in mouse bone marrow are located in specialized  niches as single cells. During homeostasis, signals from this  environment keep some HSCs dormant, which preserves long-term  self-renewal potential, while other HSCs actively self renew to maintain  haematopoiesis. In response to haematopoietic stress, dormant HSCs  become activated and rapidly replenish the haematopoietic system.  Interestingly, three factors — granulocyte colony-stimulating factor,  interferon-? and arsenic trioxide — have been  shown to efficiently activate dormant stem cells and thereby could break  their resistance to anti-proliferative chemotherapeutics. Thus, we  propose that two-step strategies could target resistant leukaemic stem  cells by priming tumours with activators of dormancy followed by  chemotherapy or targeted therapies.



#22 valiantchong

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Posted 28 April 2011 - 10:55 AM

Characterization of chronic myeloid leukemia stem cells.

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Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. jgerber2@jhmi.edu

Abstract

Although tyrosine kinase inhibitors have redefined the care of chronic myeloid leukemia (CML), these agents have not proved curative, likely due to resistance of the leukemia stem cells (LSC). While a number of potential therapeutic targets have emerged in CML, their expression in the LSC remains largely unknown. We therefore isolated subsets of CD34(+) stem/progenitor cells from normal donors and from patients with chronic phase or blast crisis CML. These cell subsets were then characterized based on ability to engraft immunodeficient mice and expression of candidate therapeutic targets. The CD34(+)CD38(-) CML cell population with high aldehyde dehydrogenase (ALDH) activity was the most enriched for immunodeficient mouse engrafting capacity. The putative targets: PROTEINASE 3, SURVIVIN, and hTERT were expressed only at relatively low levels by the CD34(+)CD38(-)ALDH(high) CML cells, similar to the normal CD34(+)CD38(-)ALDH(high) cells and less than in the total CML CD34(+) cells. In fact, the highest expression of these antigens was in normal, unfractionated CD34(+) cells. In contrast, PRAME and WT1 were more highly expressed by all CML CD34(+) subsets than their normal counterparts. Thus, ALDH activity appears to enrich for CML stem cells, which display an expression profile that is distinct from normal stem/progenitor cells and even the CML progenitors. Indeed, expression of a putative target by the total CD34(+) population in CML does not guarantee expression by the LSC. These expression patterns suggest that PROTEINASE 3, SURVIVIN, and hTERT are not optimal therapeutic targets in CML stem cells; whereas PRAME and WT1 seem promising.



#23 Trey

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Posted 28 April 2011 - 11:14 AM

There are hundreds of such articles about trying to ID LSCs, and none of them come to any clinically useful conclusion.






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