Stem Cells Central To Pathogenesis Of Mature Lymphoid Tumors

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BlankStem Cells Central To Pathogenesis Of Mature Lymphoid Tumors

17 Aug 2011

New research suggests that blood stem cells can be involved in the generation of

leukemia, even when the leukemia is caused by the abnormal proliferation of

mature cells. The study, published by Cell Press in the August 16th issue of the

journal Cancer Cell, may guide future strategies aimed at identifying

therapeutic targets for chronic lymphocytic leukemia (CLL).

CLL is a cancer of a type of mature white blood cell called a B lymphocyte.

" Most human CLL cases have a precursor phase, called monoclonal B lymphocytosis

(MBL), that is an asymptomatic proliferation of B cells, " explains senior study

author Dr. Dr. Koichi Akashi from Kyushu University Graduate School of Medical

Sciences in Japan. " Our question was, if progression from MBL to CLL reflects

stepwise proliferation of aberrant cells, at what stage does the first

cancer-causing event occur? "

To look for the cell population with cancer-initiating activity in human CLL,

Dr. Akashi and colleagues tried to find the specific developmental stage where

abnormal clonal B cells first appear. They began at the beginning, with

hematopoietic stem cells (HSCs). HSCs are blood stem cells that can give rise to

any type of blood cell. The researchers purified HSCs from healthy individuals

or HSCs from CLL patients and transplanted them into mice with a deficient

immune system. In contrast to the normal HSCs, the CLL HSCs gave rise to B cells

similar to those seen in MBL. Interestingly, the CLL HSCs did not have

chromosomal abnormalities common to CLL, suggesting that acquisition of

chromosomal abnormalities that transform MBL into CLL are secondary events.

Taken together, the findings suggest that HSCs are involved in the pathogenesis

of CLL, even though CLL is a malignancy of a mature cell type. " Our data suggest

that the propensity to progress to CLL is already acquired at the HSC stage, "

concludes Dr. Akashi. " Identification of the intrinsic abnormality of HSCs in

patients with CLL should be the key to finding the ultimate therapeutic target

in human CLL. "

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Article URL: http://www.medicalnewstoday.com/releases/232813.php