Potential Relevance of B-cell Maturation Pathways in Defining the Cell(s) of Origin for Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a common, incurable disease of undefined cause. Notably, the normal cell equivalents of CLL cells remain elusive, and it is possible that the disease emanates from several normal B-cell subsets. This article reviews the literature relating to this issue, focusing on recent findings, in particular made through epigenetic analyses that strongly support the disease developing from a normal Ag-experienced and memory cell-like B lymphocyte. It also reports the known pathways whereby normal B lymphocytes mature after antigenic challenge and proposes that this information is relevant in defining the cells of origin of this disease.