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A rare subgroup of leukemia stem cells harbors relapse-inducing potential in acute lymphoblastic leukemia.
Exp. Hematol. 69, 1-10 (2019)
After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the development of relapse. The high abundance of stem-like cells in acute lymphoblastic leukemia (ALL), however, suggests that not all leukemia-initiating cells carry these adverse characteristics, complicating the biological characterization of relapse-inducing cells in this malignancy. Here, we review sources of therapy resistance and relapse in acute leukemias, which include tumor cell plasticity and reversible characteristics. We discuss the development of patient-derived mouse models that are genetically engineered to mimic long-term dormancy and minimal residual disease in patients. These models allow the tracking and functional characterization of patient-derived ALL blasts that combine the properties of long-term dormancy, treatment resistance, and sternness. Finally, we discuss possible therapeutic avenues to target the functional plasticity of leukemia-initiating cells in ALL. (C) 2018 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
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Publication type
Article: Journal article
Document type
Review
Keywords
Acute Lymphoblastic Leukemia ; Dormancy ; Leukemia Stem Cells ; Relapse ; Therapy Resistance; Acute Myeloid-leukemia; Minimal Residual Disease; Bone-marrow Niche; Self-renewal; Drug-resistance; Oxidative-phosphorylation; Mutational Landscape; Propagating Cells; Initiating Cells; Stromal Cells
ISSN (print) / ISBN
0301-472X
e-ISSN
0301-472X
Journal
Experimental Hematology
Quellenangaben
Volume: 69,
Pages: 1-10
Publisher
Elsevier
Publishing Place
360 Park Ave South, New York, Ny 10010-1710 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)