title: CXCR4 Is Required for Leukemia-Initiating Cell Activity in T Cell Acute Lymphoblastic Leukemia.
abstract: Impaired cell migration has been demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cells upon calcineurin inactivation, among other phenotypic traits including increased apoptosis, inhibition of cell proliferation, and ultimately inhibition of leukemia-initiating cell (LIC) activity. Herein we demonstrate that the chemokine receptor CXCR4 is essential to the LIC activity of T-ALL leukemic cells both in NOTCH-induced mouse T-ALL and human T-ALL xenograft models. We further demonstrate that calcineurin regulates CXCR4 cell-surface expression in a cortactin-dependent manner, a mechanism essential to the migratory properties of T-ALL cells. Because 20%-25% of pediatric and over 50% of adult patients with T-ALL do not achieve complete remission and relapse, our results call for clinical trials incorporating CXCR4 antagonists in T-ALL treatment.
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France. Electronic address: diana.passaro@crick.ac.uk.
authors.forename: Diana
authors.initials: D
authors.lastname: Passaro
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France.
authors.forename: Marta
authors.initials: M
authors.lastname: Irigoyen
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Catherinet
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gachet
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Da Costa De Jesus
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Lasgi
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Tran Quang
authors.affiliation: Institut Curie, Centre Universitaire, Bat 110, 91405 Orsay, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3306, Centre Universitaire, Bat 110, 91405 Orsay, France; Institut National de la Santé et de la Recherche Médicale, Unité 1005, Centre Universitaire, Bat 110, 91405 Orsay, France. Electronic address: jacques.ghysdael@curie.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Ghysdael
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019703:Calcineurin / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C527276:CXCR4 protein, human; C514936:CXCR4 protein, mouse; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D019718:Receptors, CXCR4; D019703:Calcineurin