title: Early relapse in ALL is identified by time to leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways.
abstract: 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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany. lueder-hinrich.meyer@uniklinik-ulm.de
authors.forename: Lüder Hinrich
authors.initials: LH
authors.lastname: Meyer
authors.forename: Sarah Mirjam
authors.initials: SM
authors.lastname: Eckhoff
authors.forename: Manon
authors.initials: M
authors.lastname: Queudeville
authors.forename: Johann Michael
authors.initials: JM
authors.lastname: Kraus
authors.forename: Marco
authors.initials: M
authors.lastname: Giordan
authors.forename: Jana
authors.initials: J
authors.lastname: Stursberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Zangrando
authors.forename: Elena
authors.initials: E
authors.lastname: Vendramini
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Andre
authors.initials: A
authors.lastname: Schrauder
authors.forename: Georgia
authors.initials: G
authors.lastname: Lahr
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Karsten
authors.initials: K
authors.lastname: Stahnke
authors.forename: Hans Armin
authors.initials: HA
authors.lastname: Kestler
authors.forename: Geertruy
authors.initials: G
authors.lastname: Te Kronnie
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D012008:Recurrence; D016019:Survival Analysis; D014183:Transplantation, Heterologous