Stem Cells Central To Pathogenesis Of Mature Lymphoid Tumors

In a study published in the August 16 issue of the journal Cancer Cell, researchers report that although abnormal proliferation of mature cells causes leukemia, blood stem cells could be implicated for their involvement in the development of leukemia.

The study may provide new insights into developing future strategies focused on recognizing therapeutic targets for chronic lymphocytic leukemia (CLL).

The cancer of a mature white blood cell known as B lymphocyte causes CLL. Senior study author Dr. Dr. Koichi Akashi from Kyushu University Graduate School of Medical Sciences in Japan explains, “Most human CLL cases have a precursor phase, called monoclonal B lymphocytosis (MBL), that is an asymptomatic proliferation of B cells.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?”

Dr. Akashi and colleagues tried to scout for a cell population in human CLL having cancer-initiating activity. To achieve this, they attempted to identify the specific developmental stage at which abnormal clonal B cells make their first appearance. They first targeted hematopoietic stem cells (HSCs), which are blood stem cells that can give rise to any type of blood cell. HSCs taken from CLL patients or HSCs purified from healthy individuals were inserted into immune-deficient mice. The researchers found that contrary to the normal HSCs, the CLL HSCs produced B cells identical to those seen in MBL. It was fascinating to note that chromosomal abnormalities common to CLL were not present in the CLL HSCs which implied that transformation of MBL into CLL through the acquisition of chromosomal abnormalities is a secondary event.

Although CLL is a malignancy of a mature cell type, the findings propose that pathogenesis of CLL id caused by the involvement of HSCs. To conclude, Dr. Akashi said, “Our data suggest that the propensity to progress to CLL is already acquired at the HSC stage. Identification of the intrinsic abnormality of HSCs in patients with CLL should be the key to finding the ultimate therapeutic target in human CLL.”