Fig. 2

The Properties of Stochastic Stem Cells in B Cell Malignancies. In B cell malignancies the main cancer mutational events occur during VDJ recombination and somatic hypermutation. The resultant malignant cells that arise during B cell development remain fixed at that point in development and neither progress to be terminally differentiated plasma cell or undergo apoptotic death as B cells that fail developmental checks normally do. Dependant on the timing of the onset of the malignant phenotype the B cell takes on the phenotype of the cell of origin. Each of the malignant cell types are developmentally isolated from the HSC but can develop stochastic cells with stem like qualities, including a degree of resistance to chemotherapy. We suggest that there is a balance of this stem like acquired chemotherapy resistance against the apoptotic sensitivity linked to the upregulated activity in B cell development related to VDJ and SHM activity. This balance determines if the differing stochastic stem cells will survive chemotherapy and hence if the B cell malignancy can have the potential to be cured with chemotherapy or not