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New Approaches to Target Leukemia Stem Cells
Annals of Oncology 25 (Supplement 5): v14–v16, 2014 doi:10.1093/annonc/mdu407.9
Educational Lecture EL22
NEW APPROACHES TO TARGET LEUKEMIA STEM CELLS
abstracts
Human acute myeloid leukemia is organized as a hierarchy initiated and maintained by leukemia stem cells (LSC) which possesses self-renewal capacity. LSCs are therapeutic targets and must be eliminated to cure the patients. Acute myeloid leukemia (AML) follows a cancer stem cell model and organized from LSCs defined by using a sensitive
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_5/v15/2240148 by guest on 24 October 2019
Katsuto Takenaka Center for Cellular and Molecular Medicine, Kyushu University Hospital
xenograft assay. Analysis of gene expression from functionally validated LSC populations and normal hematopoietic stem cells (HSCs) yielded an LSC- and HSCspecific gene signatures, respectively. Bioinformatic analysis identified a core transcriptional program shared by LSCs and HSCs, revealing the molecular machinery underlying stemness properties. Both stem cell programs are highly significant independent predictors of patient survival and are found in existing prognostic signatures. Thus, determinants of stemness influence the clinical outcome of AML, establishing that LSCs are clinically relevant and not artifacts of xenotransplantation. Recent advances in LSC research provided insights into the cell surface antigens preferentially expressed on AML-LSCs compared with normal hematopoietic stem cells and the signaling pathways defining the LSC characteristics. These molecules are potential targets to eradicate LSCs. Especially, monoclonal antibodies targeting surface antigens expressed on LSCs, including CD123, CD44, TIM-3 and CD47 have been shown its efficacy against AML-LSCs in xenotransplant models.
Educational Lecture EL22
NEW APPROACHES TO TARGET LEUKEMIA STEM CELLS
abstracts
Human acute myeloid leukemia is organized as a hierarchy initiated and maintained by leukemia stem cells (LSC) which possesses self-renewal capacity. LSCs are therapeutic targets and must be eliminated to cure the patients. Acute myeloid leukemia (AML) follows a cancer stem cell model and organized from LSCs defined by using a sensitive
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_5/v15/2240148 by guest on 24 October 2019
Katsuto Takenaka Center for Cellular and Molecular Medicine, Kyushu University Hospital
xenograft assay. Analysis of gene expression from functionally validated LSC populations and normal hematopoietic stem cells (HSCs) yielded an LSC- and HSCspecific gene signatures, respectively. Bioinformatic analysis identified a core transcriptional program shared by LSCs and HSCs, revealing the molecular machinery underlying stemness properties. Both stem cell programs are highly significant independent predictors of patient survival and are found in existing prognostic signatures. Thus, determinants of stemness influence the clinical outcome of AML, establishing that LSCs are clinically relevant and not artifacts of xenotransplantation. Recent advances in LSC research provided insights into the cell surface antigens preferentially expressed on AML-LSCs compared with normal hematopoietic stem cells and the signaling pathways defining the LSC characteristics. These molecules are potential targets to eradicate LSCs. Especially, monoclonal antibodies targeting surface antigens expressed on LSCs, including CD123, CD44, TIM-3 and CD47 have been shown its efficacy against AML-LSCs in xenotransplant models.