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Molecules 2018, 23(8), 2060; https://doi.org/10.3390/molecules23082060

Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches

1
Laboratory of Molecular Haematopoiesis and Stem Cell Biology, Department of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy
2
Laboratory of Medical Oncology, Department of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy
3
Tecnologica Research Institute-Marrelli Hospital, 88900 Crotone, Italy
4
German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
*
Authors to whom correspondence should be addressed.
Received: 16 July 2018 / Revised: 9 August 2018 / Accepted: 14 August 2018 / Published: 17 August 2018
(This article belongs to the Special Issue Gene Delivery)
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Abstract

Acute myeloid leukemia (AML), the most common acute leukemia in the adult, is believed to arise as a consequence of multiple molecular events that confer on primitive hematopoietic progenitors unlimited self-renewal potential and cause defective differentiation. A number of genetic aberrations, among which a variety of gene fusions, have been implicated in the development of a transformed phenotype through the generation of dysfunctional molecules that disrupt key regulatory mechanisms controlling survival, proliferation, and differentiation in normal stem and progenitor cells. Such genetic aberrations can be recreated experimentally to a large extent, to render normal hematopoietic stem cells “bad”, analogous to the leukemic stem cells. Here, we wish to provide a brief outline of the complementary experimental approaches, largely based on gene delivery and more recently on gene editing, employed over the last two decades to gain insights into the molecular mechanisms underlying AML development and progression and on the prospects that their applications offer for the discovery and validation of innovative therapies. View Full-Text
Keywords: acute myeloid leukemia; chromosomal translocations; genetic aberrations; genome editing; leukemia stem cells; viral vectors; xenotransplants acute myeloid leukemia; chromosomal translocations; genetic aberrations; genome editing; leukemia stem cells; viral vectors; xenotransplants
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. (CC BY 4.0).
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Mesuraca, M.; Amodio, N.; Chiarella, E.; Scicchitano, S.; Aloisio, A.; Codispoti, B.; Lucchino, V.; Montalcini, Y.; Bond, H.M.; Morrone, G. Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches. Molecules 2018, 23, 2060.

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