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Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia.
Churchman, Michelle L; Low, Jonathan; Qu, Chunxu; Paietta, Elisabeth M; Kasper, Lawryn H; Chang, Yunchao; Payne-Turner, Debbie; Althoff, Mark J; Song, Guangchun; Chen, Shann-Ching; Ma, Jing; Rusch, Michael; McGoldrick, Dan; Edmonson, Michael; Gupta, Pankaj; Wang, Yong-Dong; Caufield, William; Freeman, Burgess; Li, Lie; Panetta, John C; Baker, Sharyn; Yang, Yung-Li; Roberts, Kathryn G; McCastlain, Kelly; Iacobucci, Ilaria; Peters, Jennifer L; Centonze, Victoria E; Notta, Faiyaz; Dobson, Stephanie M; Zandi, Sasan; Dick, John E; Janke, Laura; Peng, Junmin; Kodali, Kiran; Pagala, Vishwajeeth; Min, Jaeki; Mayasundari, Anand; Williams, Richard T; Willman, Cheryl L; Rowe, Jacob; Luger, Selina; Dickins, Ross A; Guy, R Kiplin; Chen, Taosheng; Mullighan, Charles G.
Afiliación
  • Churchman ML; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Low J; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Qu C; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Paietta EM; Department of Medicine, Montefiore Medical Center, North Division, Bronx, NY 10466, USA.
  • Kasper LH; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Chang Y; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Payne-Turner D; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Althoff MJ; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Song G; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Chen SC; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Ma J; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Rusch M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • McGoldrick D; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Edmonson M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Gupta P; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Wang YD; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Caufield W; Preclinical Pharmacokinetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Freeman B; Preclinical Pharmacokinetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Li L; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Panetta JC; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Baker S; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Yang YL; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Roberts KG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • McCastlain K; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Iacobucci I; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Peters JL; Department of Cellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Centonze VE; Department of Cellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Notta F; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Dobson SM; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Zandi S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Dick JE; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Janke L; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Peng J; Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Kodali K; St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Pagala V; St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Min J; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Mayasundari A; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Williams RT; Puma Biotechnology, Los Angeles, CA 90024, USA.
  • Willman CL; Department of Pathology, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA.
  • Rowe J; Hematology, Shaare Zedek Medical Center, 9103102 Jerusalem, Israel.
  • Luger S; Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Dickins RA; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Guy RK; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Chen T; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: charles.mullighan@stjude.org.
Cancer Cell ; 28(3): 343-56, 2015 Sep 14.
Article en En | MEDLINE | ID: mdl-26321221
Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retinoides / Proteínas de Fusión bcr-abl / Factor de Transcripción Ikaros / Leucemia-Linfoma Linfoblástico de Células Precursoras / Mutación Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retinoides / Proteínas de Fusión bcr-abl / Factor de Transcripción Ikaros / Leucemia-Linfoma Linfoblástico de Células Precursoras / Mutación Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos