T-cell leukemogenesis is an inappropriate lineage decision-making process: implications for precision oncology

Guillermo Rodríguez-Hernández; Sanil Bhatia; Carolina Vicente-Dueñas; Arndt Borkhardt; Julia Hauer; Isidro Sánchez-García

doi:10.1080/23723556.2018.1497860

T-cell leukemogenesis is an inappropriate lineage decision-making process: implications for precision oncology

Mol Cell Oncol. 2018 Aug 7;5(4):e1497860. doi: 10.1080/23723556.2018.1497860. eCollection 2018.

Authors

Guillermo Rodríguez-Hernández^{1

2}, Sanil Bhatia³, Carolina Vicente-Dueñas², Arndt Borkhardt³, Julia Hauer³, Isidro Sánchez-García^{1

2}

Affiliations

¹ Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Salamanca, Spain.
² Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
³ Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany.

Abstract

Genetic lineage tracing in cell type-specific mouse models of T-cell acute lymphoblastic leukemia (T-ALL) have revealed that tumor cell identity is imposed by expression of the oncogene Lim Domain Only 2 (LMO2), rather than by the target cell phenotype. This approach allowed to identify that secondary genomic alterations, like Notch1 mutations, appeared late and only took place within the thymus during T-ALL development. These concepts are therefore critical for the development of modern therapies aimed at curing T-ALL.

Keywords: Lmo2; Notch1; cancer; cancer cell-of-origin; cancer-stem-cell and tumor reprogramming; mouse models; stem cells; target cell.

Grants and funding

This work was supported by the the German Cancer Aid (Project 110997 and Translational Oncology Program 70112951); German Carreras Foundation; [DJCLS 02R/2016]; the Kinderkrebsstiftung (2016/17); Elterninitiative Kinderkrebsklinik e.V. Düsseldorf; German Children’s Cancer Foundation; Federal Ministry of Education and Research; FEDER; MINECO; [SAF2012-32810]; [SAF2015-64420-R]; [SAF2014-57791-REDC]; Junta de Castilla y León; [BIO/SA51/15]; [CSI001U14]; [UIC-017]; [CSI001U16]; European Union; German Carreras Foundation; [DJCLS R13/26]; FSE-Conserjería de Educación de la Junta de Castilla y León; [CSI001-15]; FEDER, “Miguel Servet”; [CP14/00082 - AES 2013-2016]; Instituto de Salud Carlos III (Ministerio de Economía y Competitividad); Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III; [PI17/00167]; Lady Tata International Award for Research in Leukaemia 2016-2017.