Based on our previous finding that distinct engraftment phenotypes of leukemic blasts from pediatric patients with acute lymphoblastic leukemia (ALL) xenotransplanted in NOD/SCID/huALL mice are closely associated with patient survival, the following main issues will be addressed: (1) characterization of the engraftment phenotype on genomic and miRNA levels, functional investigation of previously identified genes and attributed pathways such as apoptosis; (2) utility of the previously identified gene signature as diagnostic classifier for (early) relapse; and (3) pre-clinical testing of novel, directed treatment strategies targeting signaling molecules or pathways identified under aims (1) and (2).
The NOD/SCID/huALL xenotransplant model: characterization and prognostic impact of distinct engraftment properties (time to leukemia, TTL) of primary ALL cells
Meyer LH, Eckhoff SM, Queudeville M, Kraus JM, Giordan M, Stursberg J, Zangrando A, Vendramini E, Moricke A, Zimmermann M, Schrauder A, Lahr G, Holzmann K, Schrappe M, Basso G, Stahnke K, Kestler HA, Te Kronnie G, Debatin KM. Early relapse in ALL is identified by time to leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways. Cancer Cell. 2011;19:206-17.
Meyer LH, Debatin KM. Diversity of Human Leukemia Xenograft Mouse Models: Implications for Disease Biology. Cancer Res. 2011;71: Published Online First November 16, 2011.
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