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dc.contributor.authorKuek, V.
dc.contributor.authorHughes, A.M.
dc.contributor.authorKotecha, Rishi
dc.contributor.authorCheung, Laurence
dc.date.accessioned2021-07-27T23:25:28Z
dc.date.available2021-07-27T23:25:28Z
dc.date.issued2021
dc.identifier.citationKuek, V. and Hughes, A.M. and Kotecha, R.S. and Cheung, L.C. 2021. Therapeutic targeting of the leukaemia microenvironment. International Journal of Molecular Sciences. 22 (13): Article No. 6888.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/84773
dc.identifier.doi10.3390/ijms22136888
dc.description.abstract

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.

dc.languageeng
dc.relation.sponsoredbyhttp://purl.org/au-research/grants/nhmrc/1142627
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectbone marrow microenvironment
dc.subjectendothelial cell
dc.subjectleukaemia
dc.subjectmesenchymal stem cell
dc.subjectosteoblast
dc.subjectosteoclast
dc.subjecttherapeutic agents
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectBone Marrow Cells
dc.subjectHumans
dc.subjectLeukemia
dc.subjectSignal Transduction
dc.subjectTumor Microenvironment
dc.titleTherapeutic targeting of the leukaemia microenvironment
dc.typeJournal Article
dcterms.source.volume22
dcterms.source.number13
dcterms.source.issn1661-6596
dcterms.source.titleInternational Journal of Molecular Sciences
dc.date.updated2021-07-27T23:25:28Z
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.departmentCurtin Medical School
curtin.accessStatusOpen access
curtin.facultyFaculty of Health Sciences
curtin.contributor.orcidCheung, Laurence [0000-0001-6298-5288]
curtin.contributor.orcidKotecha, Rishi [0000-0003-1836-4075]
dcterms.source.eissn1422-0067
curtin.contributor.scopusauthoridCheung, Laurence [56663936300]


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