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Moving Myeloid Leukemia Drug Discovery Into the Third Dimension

The development of therapies aimed at leukemia has progressed substantially in the past years but childhood acute myeloid leukemia (AML) remains one of the most challenging cancers to treat. Genomic profiling of AML has greatly enhanced our understanding of the genetic and epigenetic landscape of th...

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Autores principales: Cartledge Wolf, Donna M., Langhans, Sigrid A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682595/
https://www.ncbi.nlm.nih.gov/pubmed/31417884
http://dx.doi.org/10.3389/fped.2019.00314
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author Cartledge Wolf, Donna M.
Langhans, Sigrid A.
author_facet Cartledge Wolf, Donna M.
Langhans, Sigrid A.
author_sort Cartledge Wolf, Donna M.
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description The development of therapies aimed at leukemia has progressed substantially in the past years but childhood acute myeloid leukemia (AML) remains one of the most challenging cancers to treat. Genomic profiling of AML has greatly enhanced our understanding of the genetic and epigenetic landscape of this high-risk leukemia. With it comes the opportunity to develop targeted therapies that are expected to be more effective and less toxic than current treatment regimens. Nevertheless, often overlooked in leukemia drug discovery are the dynamic interactions between leukemic cells and the bone marrow environment. The interplay between leukemic cells, stromal cells and the extracellular matrix plays critical roles in the development, progression and relapse of AML as well as in drug response and the development of resistance. Here we will review pediatric leukemia with a special focus on acute myeloid disease in children, and discuss the tumor microenvironment in the context of drug resistance and leukemia stem cell survival. We will emphasize how three-dimensional (3D) cell-based drug discovery may offer hope for both the identification and advancement of more effective treatment options for patients suffering from this devastating disease.
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spelling pubmed-66825952019-08-15 Moving Myeloid Leukemia Drug Discovery Into the Third Dimension Cartledge Wolf, Donna M. Langhans, Sigrid A. Front Pediatr Pediatrics The development of therapies aimed at leukemia has progressed substantially in the past years but childhood acute myeloid leukemia (AML) remains one of the most challenging cancers to treat. Genomic profiling of AML has greatly enhanced our understanding of the genetic and epigenetic landscape of this high-risk leukemia. With it comes the opportunity to develop targeted therapies that are expected to be more effective and less toxic than current treatment regimens. Nevertheless, often overlooked in leukemia drug discovery are the dynamic interactions between leukemic cells and the bone marrow environment. The interplay between leukemic cells, stromal cells and the extracellular matrix plays critical roles in the development, progression and relapse of AML as well as in drug response and the development of resistance. Here we will review pediatric leukemia with a special focus on acute myeloid disease in children, and discuss the tumor microenvironment in the context of drug resistance and leukemia stem cell survival. We will emphasize how three-dimensional (3D) cell-based drug discovery may offer hope for both the identification and advancement of more effective treatment options for patients suffering from this devastating disease. Frontiers Media S.A. 2019-07-30 /pmc/articles/PMC6682595/ /pubmed/31417884 http://dx.doi.org/10.3389/fped.2019.00314 Text en Copyright © 2019 Cartledge Wolf and Langhans. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Cartledge Wolf, Donna M.
Langhans, Sigrid A.
Moving Myeloid Leukemia Drug Discovery Into the Third Dimension
title Moving Myeloid Leukemia Drug Discovery Into the Third Dimension
title_full Moving Myeloid Leukemia Drug Discovery Into the Third Dimension
title_fullStr Moving Myeloid Leukemia Drug Discovery Into the Third Dimension
title_full_unstemmed Moving Myeloid Leukemia Drug Discovery Into the Third Dimension
title_short Moving Myeloid Leukemia Drug Discovery Into the Third Dimension
title_sort moving myeloid leukemia drug discovery into the third dimension
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682595/
https://www.ncbi.nlm.nih.gov/pubmed/31417884
http://dx.doi.org/10.3389/fped.2019.00314
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