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Stem Cells International
Volume 2015, Article ID 137164, 13 pages
http://dx.doi.org/10.1155/2015/137164
Review Article

Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia

1Department of Hematology/Oncology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
2LOEWE Center for Cell and Gene Therapy Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
3German Cancer Consortium (DKTK), Heidelberg, Germany
4German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

Received 17 April 2015; Revised 16 June 2015; Accepted 17 June 2015

Academic Editor: Franca Fagioli

Copyright © 2015 Fabian Lang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients’ outcome in ALL.