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Author
Alpar, D.; Wren, D.; Ermini, L.; Mansur, M.B.; van Delft, F.W.; Bateman, C.M.; Titley, I.; Kearney, L.; Szczepanski, T.; de Castro, D.G.; Ford, A.M.; Potter, N.E.; Greaves, M.
Title
Clonal origins of ETV6-RUNX1 acute lymphoblastic leukemia: studies in monozygotic twins
Type
Journal Article
Year
2014
Publication
Leukemia
Abbreviated Journal
Leukemia
Volume
Issue
Pages
Keywords
Abstract
Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, pre-natal genetic event with other driver aberrations occurring subclonally and probably post-natally. 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 V(D)J 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.Leukemia accepted article preview online, 12 November 2014. doi:10.1038/leu.2014.322.
Address
Centre for Evolution and Cancer, The Institute of Cancer Research – London, London, UK
Corporate Author
Thesis
Publisher
Place of Publication
Editor
Language
English
Summary Language
Original Title
Series Editor
Series Title
Abbreviated Series Title
Series Volume
Series Issue
Edition
ISSN
0887-6924
ISBN
Medium
Area
Expedition
Conference
Notes
PMID:25388957
Approved
no
Call Number
CBM.UAM @ ccobaleda @
Serial
542
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