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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6222541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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