title: Iron chelation: an adjuvant therapy to target metabolism, growth and survival of murine PTEN-deficient T lymphoma and human T lymphoblastic leukemia/lymphoma.
abstract: Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis. Interestingly, DFO displayed synergistic activity with three ALL-specific drugs: dexamethasone, doxorubicin, and L-asparaginase. DFO appeared to act through a reactive oxygen species-dependent DNA damage response and potentiated the action of an inhibitor of the PARP pathway of DNA repair. Our results demonstrate that targeting iron metabolism could be an interesting adjuvant therapy for acute lymphoblastic leukemia.
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.|c Centre Hospitalier Universitaire de Nice, Service d'Oncologie Pédiatrique, Hôpital de l'Archet , Nice , France.
authors.forename: Joy
authors.initials: J
authors.lastname: Benadiba
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Celia
authors.initials: C
authors.lastname: Rosilio
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Nebout
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Vera
authors.initials: V
authors.lastname: Heimeroth
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Zouhour
authors.initials: Z
authors.lastname: Neffati
authors.affiliation: b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.|d CNRS, Institut de Pharmacologie Moléculaire et Cellulaire , Sophia-Antipolis, Valbonne, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Popa
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Mary
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Griessinger
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Imbert
authors.affiliation: e UAM Hématologie et Oncologie Pédiatriques, Centre Hospitalier Régional Universitaire de Montpellier, Hôpital Arnaud de Villeneuve , Nice , France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.affiliation: a INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe 4 Inflammation, Cancer, Cellules Souches Cancéreuses , Nice , France.|b UFR Médecine, Faculté de Médecine , Université de Nice-Sophia Antipolis , Nice , France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Peyron
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001215:Asparaginase / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant; D004249:DNA Damage; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D017382:Reactive Oxygen Species / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D007501:Iron; D051059:PTEN Phosphohydrolase; D001215:Asparaginase; D003676:Deferoxamine
keywords: Iron metabolism; addiction; chemotherapy; leukemia; synergy