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Stem cells central to pathogenesis of mature lymphoid tumors

Date:
August 16, 2011
Source:
Cell Press
Summary:
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 may guide future strategies aimed at identifying therapeutic targets for chronic lymphocytic leukemia.

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. 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."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yoshikane Kikushige, Fumihiko Ishikawa, Toshihiro Miyamoto, Takahiro Shima, Shingo Urata, Goichi Yoshimoto, Yasuo Mori, Tadafumi Iino, Takuji Yamauchi, Tetsuya Eto, Hiroaki Niiro, Hiromi Iwasaki, Katsuto Takenaka, Koichi Akashi. Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia. Cancer Cell, 2011; 20 (2): 246-259 DOI: 10.1016/j.ccr.2011.06.029

Cite This Page:

Cell Press. "Stem cells central to pathogenesis of mature lymphoid tumors." ScienceDaily. ScienceDaily, 16 August 2011. <www.sciencedaily.com/releases/2011/08/110815121521.htm>.
Cell Press. (2011, August 16). Stem cells central to pathogenesis of mature lymphoid tumors. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2011/08/110815121521.htm
Cell Press. "Stem cells central to pathogenesis of mature lymphoid tumors." ScienceDaily. www.sciencedaily.com/releases/2011/08/110815121521.htm (accessed October 21, 2014).

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