Journal
CANCER CELL
Volume 19, Issue 2, Pages 206-217Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2010.11.014
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Funding
- European Hematology Association
- Graduate School of Mathematical Analysis of Evolution, Information and Complexity at the University of Ulm
- Citta della Speranza, Padova
- Associazione Italiana per la Ricerca sul Cancro
- Ministero dell' Universita e della Ricerca
- German Research Foundation (Deutsche Forschungsgemeinschaft) [STA555-3]
- Wilhelm Sander Foundation [2005.075.2]
- German federal ministry of education and research (BMBF) [PKB-01GS08]
- Programmi di ricerca di Rilevante Interesse Nazionale
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We investigated the engraftment properties and impact on patient outcome of 50 pediatric acute lymphoblastic leukemia (ALL) samples transplanted into NOD/SCID mice. Time to leukemia (TTL) was determined for each patient sample engrafted as weeks from transplant to overt leukemia. Short TTL was strongly associated with high risk for early relapse, identifying an independent prognostic factor. This high-risk phenotype is reflected by a gene signature that upon validation in an independent patient cohort (n = 197) identified a high-risk cluster of patients with early relapse. Furthermore, the signature points to independent pathways, including mTOR, involved in cell growth and apoptosis. The pathways identified can directly be targeted, thereby offering additional treatment approaches for these high-risk patients.
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