Project description:This SuperSeries is composed of the following subset Series: GSE28460: Expression data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases GSE28461: Promoter methylation data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases Refer to individual Series
Project description:Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis-relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A, and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell. In contrast, deletions and nonsense mutations in IKZF1 (IKAROS), were highly enriched and consistently preserved at the time of relapse. A targeted copy number screen in an unselected cohort of 131 precursor B-ALL cases, enrolled in the dexamethasone-based Dutch Childhood Oncology Group treatment protocol ALL9, revealed that IKZF1 deletions are significantly associated with poor relapse-free and overall survival rates. Separate analysis of ALL9-treatment subgroups revealed that non-high-risk patients with IKZF1 deletions exhibited a ~12-fold higher relative relapse rate than those without IKZF1 deletions. Consequently, IKZF1 deletion status allowed the prospective identification of 53% of the relapse-prone non-high-risk-classified patients within this subgroup and, therefore, serves as one of the strongest predictors of relapse at the time of diagnosis with high potential for future risk stratification. Affymetrix NspI 250k array data of 34 paired diagnosis and relapse samples of pediatric ALL. From 13 patients a complete remission sample was available. Four cases had 2 relapses.
Project description:The development of a clinically relevant xenograft model of pediatric acute lymphoblastic leukemia, using a 4-drug treatment regimen designed to mimic pediatric remission induction therapy. Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. This study was designed to establish a preclinical model of resistance to induction therapy in childhood T-ALL to examine the emergence of drug resistance and identify novel therapies. We performed transcription profiling by array of human CD45-positive human lymphocytes from patients with acute pediatric lymphoblastic leukemia, and from xenografted NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Several different treatment regimes were used in this study (VLXD, VLXDR, VLXD2, VXL and VLXD2-ALL31) and are summarised in the protocols associated with this submission.