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

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, amon...

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Autores principales: Mesuraca, Maria, Amodio, Nicola, Chiarella, Emanuela, Scicchitano, Stefania, Aloisio, Annamaria, Codispoti, Bruna, Lucchino, Valeria, Montalcini, Ylenia, Bond, Heather M., Morrone, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222541/
https://www.ncbi.nlm.nih.gov/pubmed/30126100
http://dx.doi.org/10.3390/molecules23082060
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author Mesuraca, Maria
Amodio, Nicola
Chiarella, Emanuela
Scicchitano, Stefania
Aloisio, Annamaria
Codispoti, Bruna
Lucchino, Valeria
Montalcini, Ylenia
Bond, Heather M.
Morrone, Giovanni
author_facet Mesuraca, Maria
Amodio, Nicola
Chiarella, Emanuela
Scicchitano, Stefania
Aloisio, Annamaria
Codispoti, Bruna
Lucchino, Valeria
Montalcini, Ylenia
Bond, Heather M.
Morrone, Giovanni
author_sort Mesuraca, Maria
collection PubMed
description 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.
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spelling pubmed-62225412018-11-13 Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches Mesuraca, Maria Amodio, Nicola Chiarella, Emanuela Scicchitano, Stefania Aloisio, Annamaria Codispoti, Bruna Lucchino, Valeria Montalcini, Ylenia Bond, Heather M. Morrone, Giovanni Molecules Review 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. MDPI 2018-08-17 /pmc/articles/PMC6222541/ /pubmed/30126100 http://dx.doi.org/10.3390/molecules23082060 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mesuraca, Maria
Amodio, Nicola
Chiarella, Emanuela
Scicchitano, Stefania
Aloisio, Annamaria
Codispoti, Bruna
Lucchino, Valeria
Montalcini, Ylenia
Bond, Heather M.
Morrone, Giovanni
Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches
title Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches
title_full Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches
title_fullStr Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches
title_full_unstemmed Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches
title_short Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches
title_sort turning stem cells bad: generation of clinically relevant models of human acute myeloid leukemia through gene delivery- or genome editing-based approaches
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222541/
https://www.ncbi.nlm.nih.gov/pubmed/30126100
http://dx.doi.org/10.3390/molecules23082060
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