Leukemia stem cells have more in common with embryonic stem cells 
than adult stem cells

<http://www.physorg.com/news153059231.html>http://www.physorg.com/news153059231.html
 

<http://www.physorg.com/archive/05-02-2009/>February 5th, 2009 in 
<http://www.physorg.com/science-news/>General Science / 
<http://www.physorg.com/science-news/biology/>Biology

Research using a mouse model of human leukemia has provided critical 
insight into the genetic factors related to the generation and 
maintenance of myeloid leukemia stem cells. The study, published by 
Cell Press in the February 6th issue of the journal Cell Stem Cell, 
is likely to have a profound impact on the future design of 
therapeutic approaches targeted against cancer stem cells.

Leukemia stem cells (LSCs) were initially described as rare cells 
that share characteristics with normal hematopoietic stem cells 
(HSCs). HSCs are a type of partially committed adult stem cells that 
can give rise to multiple types of blood cells. However, recent 
research has demonstrated that LSCs can represent a significant 
fraction of leukemic cells and exhibit characteristics associated 
with more mature, differentiated myeloid cells rather than the more 
versatile HSCs.

"Since LSCs may be more numerous and mature than originally proposed, 
the nature and generality of the hierarchical organization of 
malignancies has recently been questioned," says senior study author 
Dr. Michael L. Cleary, from the Department of Pathology at Stanford 
University. Dr. Cleary and colleagues used a mouse model of human AML 
to investigate the genes that maintain LSC frequencies and leukemia 
cell hierarchies.

The researchers found that LSCs are maintained in a self-renewing 
state by subversion of a transcriptional program that shares features 
with pluripotent embryonic stem cells (ESCs). This transcriptional 
program is transiently expressed in normal myeloid precursor cells 
rather than HSCs or fully mature white blood cells. The authors go on 
to reveal a link between activation of genes associated with ESCs at 
an inappropriate stage of white blood cell development, the number of 
LSCs, and a poor prognosis in leukemia.

"Importantly, the shared transcriptional features of LSCs, ESCs, 
normal mid-myeloid lineage cells, and a diverse set of poor-prognosis 
human malignancies support the broader conclusion that cancer stem 
cells may be aberrantly self-renewing downstream progenitor cells," 
explains lead study author Dr. Tim Somervaille.

The study also highlights the potential of therapeutic strategies 
aimed at genes and pathways that are of greater importance to the 
function of LSCs than HSCs. "These findings may have a substantial 
clinical impact, as normal HSCs are necessary for regeneration of 
hematopoiesis following chemotherapy," offers Dr. Cleary.

Source: Cell Press

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