1. Early Relapse in ALL Is Identified by Time to Leukemia in NOD/SCID Mice and Is Characterized by a Gene Signature Involving Survival Pathways
- Author
-
Georgia Lahr, Andrea Zangrando, Jana Stursberg, Karsten Stahnke, Anja Möricke, Karlheinz Holzmann, Giuseppe Basso, Johann M. Kraus, Martin Schrappe, Geertruy te Kronnie, Martin Zimmermann, Elena Vendramini, SM Eckhoff, André Schrauder, Klaus-Michael Debatin, Hans A. Kestler, Lüder Hinrich Meyer, Manon Queudeville, and Marco Giordan
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Transplantation, Heterologous ,Apoptosis ,Mice, SCID ,Nod ,Cohort Studies ,Mice ,Mice, Inbred NOD ,Recurrence ,Internal medicine ,medicine ,Animals ,Humans ,Child ,PI3K/AKT/mTOR pathway ,Survival analysis ,business.industry ,Gene Expression Profiling ,Infant, Newborn ,Infant ,Cell Biology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Survival Analysis ,Phenotype ,Transplantation ,Gene expression profiling ,Leukemia ,Child, Preschool ,Immunology ,Female ,business - Abstract
SummaryWe 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.
- Published
- 2011