Project description:Whole-genome GR binding sites and histone acetylation status in pediatric acute lymphoblastic leukemia patient-derived xenografts following dexamethasone treatment in vivo
Project description:We developed a model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) of acute lymphoblastic leukemia with widely-used cytotoxic drugs for 18 consecutive weeks. Transcriptome and proteome showed shared dysregulations between replicate tumors providing putative targets to overcome resistance.
Project description:Analysis of basal gene expression in patient-derived xenograft cells. A panel of pediatric ALL xenografts was utilized to further understand the biology of leukemia.
Project description:Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. The current study used a pre-clinical model of induction therapy for pediatric ALL in NOD/SCID mice (Samuels et al Blood Cancer Journal (2014) 4, e232; doi:10.1038/bcj.2014.52) to study the development of drug resistance. We performed transcription profiling by array of human CD45-positive lymphocytes from patients with acute pediatric lymphoblastic leukemia, xenografted in NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Both the primary-patient-derived and xenograft cells were analysed. The VLXD2 treatment regime is described in full in the protocols associated with this submission and in Samuels et al (Blood Cancer Journal (2014) 4, e232; doi:10.1038/bcj.2014.52). This study is an extension of E-MEXP-3916.