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