Abstract
Cancer cell heterogeneity is a feature of nearly all cancers and can be related to three major influences: (1) genetic and epigenetic heterogeneity due to clonal evolution/collapse; (2) microenvironmental influences; and (3) the underlying tissue hierarchy from which the tumor arises. Ongoing studies in whole genome sequencing and of the bone marrow, splenic and lymph node microenvironments demonstrate their contributions to tumor heterogeneity. In this chapter we will focus on the role of the hematopoietic hierarchy in blood cancer cellular heterogeneity; one of the most studied systems in mouse and human. Observations that myeloid and lymphoid malignancies harbor rare relatively quiescent therapy resistant cell populations date back over 30 years. Early studies in chronic myelogenous leukemia were consistent with a disease origin in the hematopoietic stem cell and subsequent studies have confirmed these findings. The publication by Bonnet et al. in 1994 offered the first prospective assessment of human cancer stem cell populations and established acute myeloid leukemia (AML) as a model system. In the intervening years, new technologies have allowed a continued reassessment of cancer stem cell populations in AML, myelodysplastic syndromes, multiple myeloma and acute lymphoblastic leukemia. While these studies have confirmed the existence of the rare cells capable of recapitulating the malignancy on transplantation, they have also identified considerable inter- and intra-patient heterogeneity with conflicting results on the ability to identify potential cancer stem cells using surface antigen profiles alone. Novel xenotransplantation models, whole genome sequencing and other technologies offer the tools to further refine this model in hematologic malignancies and develop rational therapies to target leukemia stem cells.
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Becker, M.W., O’Dwyer, K.M. (2015). Leukemic and Lymphoid Stem Cells. In: Babashah, S. (eds) Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-21030-8_13
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