Modeling the process of childhood ETV6-RUNX1 B-cell leukemias
Metrics: PDF 889 views | HTML 1376 views | ?
Guillermo Rodríguez-Hernández1,2, Daniel Schäfer3, Ana Gavilán1,2, Carolina Vicente-Dueñas2, Julia Hauer3, Arndt Borkhardt3,* and Isidro Sánchez-García1,2,*
1Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/ Universidad de Salamanca, Campus M. de Unamuno s/n, Salamanca, Spain
2Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
3Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Düsseldorf, Medical Faculty, Düsseldorf, Germany
*These authors considered as equal senior author
Arndt Borkhardt, email: Arndt.Borkhardt@med.uni-duesseldorf.de
Isidro Sanchez-Garcia, email: firstname.lastname@example.org
Keywords: epigenetic modulation, childhood leukemia, mutational pattern, GEMM, infection exposure
Received: July 12, 2017 Accepted: September 16, 2017 Published: September 27, 2017
ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. Pre-leukaemic clones carrying ETV6-RUNX1 oncogenic lesions are frequently found in neonatal cord blood, but only few ETV6-RUNX1 carriers develop pB-ALL. The highly demanding and pending challenge is to reveal the multistep natural history of ETV6-RUNX1 pB-ALL, because it can offer non-toxic prophylactic interventions to preleukemic carriers. However, the lack of a genetically engineered ETV6-RUNX1 mouse model mimicking the human pB-ALL has hampered our understanding of the pathogenesis of this disease. This rule has now been broken in a study of the effect of the ETV6-RUNX1 oncogene in cancer development in a mouse model in which oncogene expression is restricted to the stem cell compartment. In this article, we review the different attempts to model this disease, including the recent representative success stories and we discuss its potential application to both identify etiologic factors of childhood ETV6-RUNX1 pB-ALL and prevent the conversion of a preleukemic clone in an irreversible transformed state.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.