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Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis
The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transfo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ferrata Storti Foundation
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269284/ https://www.ncbi.nlm.nih.gov/pubmed/30337364 http://dx.doi.org/10.3324/haematol.2018.197004 |
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author | Le, Phuong M. Andreeff, Michael Battula, Venkata Lokesh |
author_facet | Le, Phuong M. Andreeff, Michael Battula, Venkata Lokesh |
author_sort | Le, Phuong M. |
collection | PubMed |
description | The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transform them to preleukemic, and eventually to leukemic, cells. Recent discoveries suggest that genetic alterations in bone marrow niche cells, particularly in osteogenic cells, may also cause myeloid leukemia in mouse models. The osteogenic niche, which consists of osteoprogenitors, preosteoblasts, mature osteoblasts, osteocytes and osteoclasts, has been shown to play a critical role in the maintenance and expansion of hematopoietic stem and progenitor cells as well as in their oncogenic transformation into leukemia stem/initiating cells. We have recently shown that acute myeloid leukemia cells induce osteogenic differentiation in mesenchymal stromal cells to gain a growth advantage. In this review, we discuss the role of the osteogenic niche in the maintenance of hematopoietic stem and progenitor cells, as well as in their transformation into leukemia cells. We also discuss the signaling pathways that regulate osteogenic niche-hematopoietic stem and progenitor cells or osteogenic niche-leukemic stem/initiating cell interactions in the bone marrow, together with novel approaches for therapeutically targeting these interactions. |
format | Online Article Text |
id | pubmed-6269284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-62692842018-12-13 Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis Le, Phuong M. Andreeff, Michael Battula, Venkata Lokesh Haematologica Review Article The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transform them to preleukemic, and eventually to leukemic, cells. Recent discoveries suggest that genetic alterations in bone marrow niche cells, particularly in osteogenic cells, may also cause myeloid leukemia in mouse models. The osteogenic niche, which consists of osteoprogenitors, preosteoblasts, mature osteoblasts, osteocytes and osteoclasts, has been shown to play a critical role in the maintenance and expansion of hematopoietic stem and progenitor cells as well as in their oncogenic transformation into leukemia stem/initiating cells. We have recently shown that acute myeloid leukemia cells induce osteogenic differentiation in mesenchymal stromal cells to gain a growth advantage. In this review, we discuss the role of the osteogenic niche in the maintenance of hematopoietic stem and progenitor cells, as well as in their transformation into leukemia cells. We also discuss the signaling pathways that regulate osteogenic niche-hematopoietic stem and progenitor cells or osteogenic niche-leukemic stem/initiating cell interactions in the bone marrow, together with novel approaches for therapeutically targeting these interactions. Ferrata Storti Foundation 2018-12 /pmc/articles/PMC6269284/ /pubmed/30337364 http://dx.doi.org/10.3324/haematol.2018.197004 Text en Copyright© 2018 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Review Article Le, Phuong M. Andreeff, Michael Battula, Venkata Lokesh Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
title | Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
title_full | Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
title_fullStr | Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
title_full_unstemmed | Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
title_short | Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
title_sort | osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269284/ https://www.ncbi.nlm.nih.gov/pubmed/30337364 http://dx.doi.org/10.3324/haematol.2018.197004 |
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