Therapeutic targeting of the leukaemia microenvironment
In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are co...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1142627 http://hdl.handle.net/20.500.11937/84773 |
| _version_ | 1848764683202330624 |
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| author | Kuek, V. Hughes, A.M. Kotecha, Rishi Cheung, Laurence |
| author_facet | Kuek, V. Hughes, A.M. Kotecha, Rishi Cheung, Laurence |
| author_sort | Kuek, V. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haemato-poietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukae-mic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leu-kaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia. |
| first_indexed | 2025-11-14T11:23:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-84773 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:23:15Z |
| publishDate | 2021 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-847732021-10-27T06:55:34Z Therapeutic targeting of the leukaemia microenvironment Kuek, V. Hughes, A.M. Kotecha, Rishi Cheung, Laurence bone marrow microenvironment endothelial cell leukaemia mesenchymal stem cell osteoblast osteoclast therapeutic agents Animals Antineoplastic Agents Bone Marrow Cells Humans Leukemia Signal Transduction Tumor Microenvironment In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haemato-poietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukae-mic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leu-kaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia. 2021 Journal Article http://hdl.handle.net/20.500.11937/84773 10.3390/ijms22136888 eng http://purl.org/au-research/grants/nhmrc/1142627 http://creativecommons.org/licenses/by/4.0/ fulltext |
| spellingShingle | bone marrow microenvironment endothelial cell leukaemia mesenchymal stem cell osteoblast osteoclast therapeutic agents Animals Antineoplastic Agents Bone Marrow Cells Humans Leukemia Signal Transduction Tumor Microenvironment Kuek, V. Hughes, A.M. Kotecha, Rishi Cheung, Laurence Therapeutic targeting of the leukaemia microenvironment |
| title | Therapeutic targeting of the leukaemia microenvironment |
| title_full | Therapeutic targeting of the leukaemia microenvironment |
| title_fullStr | Therapeutic targeting of the leukaemia microenvironment |
| title_full_unstemmed | Therapeutic targeting of the leukaemia microenvironment |
| title_short | Therapeutic targeting of the leukaemia microenvironment |
| title_sort | therapeutic targeting of the leukaemia microenvironment |
| topic | bone marrow microenvironment endothelial cell leukaemia mesenchymal stem cell osteoblast osteoclast therapeutic agents Animals Antineoplastic Agents Bone Marrow Cells Humans Leukemia Signal Transduction Tumor Microenvironment |
| url | http://purl.org/au-research/grants/nhmrc/1142627 http://hdl.handle.net/20.500.11937/84773 |