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Acute myeloid leukaemia (AML) remains a deadly disease, largely due to the persistence of drug-resistant leukaemia-initiating cells (LICs) which promote relapse. Therefore, effective therapies must target LICs. Patient-derived xenografts (PDXs) are valuable for testing new therapies, though establishing AML PDX models is challenging. Two humanized mouse strains, MISTRG and NRGS, have been developed for this purpose. In this study, we show both are suitable strains for the development of AML PDXs; however, MISTRG-derived PDXs contain 10 times higher LIC frequencies than NRGS-derived PDXs. These differences have crucial implications for preclinical AML therapy testing and modelling relapse models of the disease.
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http://dx.doi.org/10.1111/bjh.20029 | DOI Listing |
Br J Haematol
April 2025
Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, New South Wales, Australia.
Acute myeloid leukaemia (AML) remains a deadly disease, largely due to the persistence of drug-resistant leukaemia-initiating cells (LICs) which promote relapse. Therefore, effective therapies must target LICs. Patient-derived xenografts (PDXs) are valuable for testing new therapies, though establishing AML PDX models is challenging.
View Article and Find Full Text PDFNat Cell Biol
December 2024
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
RNA modification has emerged as an important epigenetic mechanism that controls abnormal metabolism and growth in acute myeloid leukaemia (AML). However, the roles of RNA N-acetylcytidine (ac4C) modification in AML remain elusive. Here, we report that ac4C and its catalytic enzyme NAT10 drive leukaemogenesis and sustain self-renewal of leukaemic stem cells/leukaemia-initiating cells through reprogramming serine metabolism.
View Article and Find Full Text PDFInt J Lab Hematol
October 2024
Department of Hematology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Many tumours are organised in a hierarchical structure with at its apex a cell that can maintain, establish, and repopulate the tumour-the cancer stem cell. The haematopoietic stem cell (HSC) is the founder cell for all functional blood cells. Like HSCs, the leukaemia stem cells (LSC) are hypothesised to be the leukaemia-initiating cells, which have features of stemness such as self-renewal, quiescence, and resistance to cytotoxic drugs.
View Article and Find Full Text PDFLeuk Res
September 2021
Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, Oxford, OX3 9DS, UK; Institute of Cancer Research, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, London, SM2 5NG, UK. Electronic address:
Refractory T cell acute leukaemias that no longer respond to treatment would benefit from new modalities that target T cell-specific surface proteins. T cell associated surface proteins (the surfaceome) offer possible therapy targets to reduce tumour burden but also target the leukaemia-initiating cells from which tumours recur. Recent studies of the T cell leukaemia surfaceome confirmed that CD7 is highly expressed in overt disease.
View Article and Find Full Text PDFSci Rep
March 2021
Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Regulation of haematopoietic stem cell fate through conditional gene expression could improve understanding of healthy haematopoietic and leukaemia initiating cell (LIC) biology. We established conditionally immortalised myeloid progenitor cell lines co-expressing constitutive Hoxa9.EGFP and inducible Meis1.
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