@article{004b19d6e796481db261ab288bf44dfd,
title = "Clonal origins of ETV6-RUNX1 + acute lymphoblastic leukemia: Studies in monozygotic twins",
abstract = "Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned that shared clonal rearrangements of IG or TCR genes by concordant ALL in twins would be informative about the fetal cell type in which clonal advantage is elicited by ETV6-RUNX1. Five pairs of twins were analyzed for all varieties of IG and TCR gene rearrangements. All pairs showed identical incomplete or complete variable-diversity-joining junctions coupled with substantial, subclonal and divergent rearrangements. This pattern was endorsed by single-cell genetic scrutiny in one twin pair. Our data suggest that the pre-leukemic initiating function of ETV6-RUNX1 fusion is associated with clonal expansion early in the fetal B-cell lineage.",
author = "D. Alpar and D. Wren and L. Ermini and Mansur, {M. B.} and {Van Delft}, {F. W.} and Bateman, {C. M.} and I. Titley and L. Kearney and T. Szczepanski and D. Gonzalez and Ford, {A. M.} and Potter, {N. E.} and M. Greaves",
note = "Funding Information: We would like to thank patients and families involved in this study, Prof Tim O Eden (Academic Unit of Paediatric Oncology, University of Manchester), Dr Manoo Bhakta (University of Tennessee at Chattanooga and TC Thompson Children{\textquoteright}s Hospital), Dr Eric J Gratias (University of Tennessee at Chattanooga and TC Thompson Children{\textquoteright}s Hospital), Prof Elisabeth R van Wering (Dutch Childhood Oncology Group), Dr Richard Hain (Children{\textquoteright}s Hospital for Wales), Dr Giovanni Cazzaniga (Clinica Pediatrica University di Milano Bicocca, Monza) and the Leukemia & Lymphoma Research Cellbank for providing patient samples. This research on childhood leukemic samples was conducted under ethical approval (CCR 2285 Royal Marsden Hospital NHS Foundation Trust). We are also grateful to Professor Marie-Paule Lefranc for her guidance regarding the proper IMGT nomenclature, to Daphne Webster for her excellent technical assistance and to Christopher P Wardell for providing bioinformatic support. DA is supported as an ISAC scholar by the International Society for Advancement of Cytometry. DA and The Institute of Cancer Research, and LE and the University of Copenhagen acknowledge the support of the European Commission under the Marie Curie Intra-European Fellowship Programme. The contents of this paper reflect only the authors{\textquoteright} views and not the views of the European Commission. We also acknowledge the use of services provided by The Institute of Cancer Research Genetics Core Facility, which is managed by Dr Sandra Hanks. This work was supported by Leukaemia & Lymphoma Research United Kingdom, the Kay Kendall Leukaemia Fund United Kingdom and the Gabrielle{\textquoteright}s Angel Foundation for Cancer Research and The Wellcome Trust (grant number 105104/Z/14/Z). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = apr,
day = "15",
doi = "10.1038/leu.2014.322",
language = "English",
volume = "29",
pages = "839--846",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "4",
}