CLL HSCs - implications?

[Guest guest]

In the Aug.16 issue of " Cancer Cell " , Kikushige et al.

published observations of human hematopoietic stem cells

(HSCs) from CLL patients developing (in a xenogeneic mouse

model) into mature CLL Bcells. Links are below.

The authors concluded that CLL patients have unique HSCs,

which do not exist in control subjects, that could be the

original precursor cells that eventually develop into mature

CLL Bcells.

A commentary (by Alizadeh & Majeti) in the same issue of

Cancer Cell, concludes that, 'if' this xenogeneic model

reflects the biology of the human disease, then therapeutic

targeting strategies with an objective of being curative may

be insufficient if they target biochemical characteristics

unique to mature CLL Bcells but absent from these

predecessor CLL HSCs. See the " SNIP " below.

What are other implications of the existence of CLL HSCs?

For example, what roles might they play in recurrence of CLL

disease after remissions?

PRESS RELEASE:

Stem Cells Central to Pathogenesis of Mature Lymphoid Tumors

http://www.sciencedaily.com/releases/2011/08/110815121521.htm

ORIGINAL RESEARCH PAPER:

" Self-Renewing Hematopoietic Stem Cell Is the Primary Target

in Pathogenesis of Human Chronic Lymphocytic Leukemia " ; Y.

Kikushige et al.; Cancer Cell 20, 246–259, August 16, 2011

http://www.cell.com/cancer-cell/retrieve/pii/S1535610811002595I

COMMENTARY:

" Surprise! HSC Are Aberrant in Chronic Lymphocytic Leukemia "

Ash A. Alizadeh and Ravindra Majeti Cancer Cell 20,

August 16, 2011 135-136

http://www.sciencedirect.com/science/article/pii/S1535610811002698

SNIP......

" Nearly all current therapies for CLL, including rituximab,

target the mature B cell leukemic population; however, it

may be that therapies effective at targeting these CLL cells

will not affect the preleukemic HSC. Thus, curative

strategies may need to target not only the frankly leukemic

cells, but also the preleukemic HSC. How to preferentially

target these preleukemic HSC, as compared to residual normal

HSC, represents a major challenge that will depend on

investigations into the mechanisms that give rise to these

aberrant cells. "

Al Janski