title: Bringing Leukemia Stem Cells into the Clinic.
abstract: Outcomes in acute myeloid leukemia (AML) remain poor due to high rates of relapse. Thus, there is an urgent unmet medical need for new therapies that can more effectively kill the leukemia stem cells (LSC) and recently recognized preleukemic hematopoietic stem cells (preL-HSC) that can drive relapsed disease. In order to develop such therapies, a better understanding of the biology of these stem cell populations is required. The best functional assays for stem cells are xenotransplantation models using immunodeficient mouse recipients. Here, we present evidence of the clinical validity of such models for studying the biology of AML stem cells and propose a new paradigm for the development of LSC-targeted agents and biomarker tools for patient selection.
authors.affiliation: Princess Margaret Cancer Research Centre, University Health Network, Toronto, Ont., Canada.
authors.forename: Jean C Y
authors.initials: JC
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D009570:Nitriles; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D053614:Janus Kinase 2; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; D011759:Pyrrolidines; D013449:Sulfonamides; C528327:fedratinib; D000096926:Benzenesulfonamides; C540383:ruxolitinib; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse