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Author  |
van Delft, F.W.; Horsley, S.; Colman, S.; Anderson, K.; Bateman, C.; Kempski, H.; Zuna, J.; Eckert, C.; Saha, V.; Kearney, L.; Ford, A.; Greaves, M. |
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Title |
Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia |
Type |
Journal Article |
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Year |
2011 |
Publication |
Blood |
Abbreviated Journal |
Blood |
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Volume |
117 |
Issue |
23 |
Pages |
6247-6254 |
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Keywords |
Child; Child, Preschool; Chromosomes, Human, Pair 16/*genetics/metabolism; Chromosomes, Human, Pair 6/*genetics/metabolism; Cyclin C; Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism; Female; Humans; Male; Oncogene Proteins, Fusion/*genetics/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/metabolism/mortality/therapy; Recurrence; *Sequence Deletion; *Translocation, Genetic |
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Abstract |
B-cell precursor childhood acute lymphoblastic leukemia with ETV6-RUNX1 (TEL-AML1) fusion has an overall good prognosis, but relapses occur, usually after cessation of treatment and occasionally many years later. We have investigated the clonal origins of relapse by comparing the profiles of genomewide copy number alterations at presentation in 21 patients with those in matched relapse (12-119 months). We identified, in total, 159 copy number alterations at presentation and 231 at relapse (excluding Ig/TCR). Deletions of CDKN2A/B or CCNC (6q16.2-3) or both increased from 38% at presentation to 76% in relapse, suggesting that cell-cycle deregulation contributed to emergence of relapse. A novel observation was recurrent gain of chromosome 16 (2 patients at presentation, 4 at relapse) and deletion of plasmocytoma variant translocation 1 in 3 patients. The data indicate that, irrespective of time to relapse, the relapse clone was derived from either a major or minor clone at presentation. Backtracking analysis by FISH identified a minor subclone at diagnosis whose genotype matched that observed in relapse approximately 10 years later. These data indicate subclonal diversity at diagnosis, providing a variable basis for intraclonal origins of relapse and extended periods (years) of dormancy, possibly by quiescence, for stem cells in ETV6-RUNX1(+) acute lymphoblastic leukemia. |
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Address |
Section of Haemato-Oncology, Institute of Cancer Research, Sutton, UK |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0006-4971 |
ISBN |
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Area |
WP6 In vivo |
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Conference |
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Notes |
PMID:21482711 |
Approved |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
49 |
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