A5050317856- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- T-cell and Retrovirus Studies
- Immune Cell Function and Interaction
- DNA and Nucleic Acid Chemistry
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Renal and related cancers
- RNA and protein synthesis mechanisms
- 14-3-3 protein interactions
- Circular RNAs in diseases
Princess Máxima Center
2016-2024
Erasmus MC - Sophia Children’s Hospital
2005-2016
Erasmus MC
2006-2014
Erasmus University Rotterdam
2006-2011
Brigham and Women's Hospital
2006
Harvard University
2006
Stichting Kinderoncologie Nederland
2006
Beatrix Kinderziekenhuis
2006
Vrije Universiteit Amsterdam
2006
PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN have been proposed as secondary that follow NOTCH1-activating cause cellular resistance to γ-secretase inhibitors.The of PTEN, PI3K AKT was studied a genetically well-characterized pediatric leukemia patient cohort (n=146) treated on DCOG or COALL protocols.PTEN E17K were detected 13% 2% patients, respectively. Defective...
Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% pediatric cases considered a high-risk disease. T-ALL often associated with resistance to treatment, including steroids, which are currently cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival cure. However, cellular mechanisms underlying patients poorly understood. In this...
We identified mutations in the IL7Ra gene or genes encoding downstream signaling molecules JAK1, JAK3, STAT5B, N-RAS, K-RAS, NF1, AKT and PTEN 49% of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Strikingly, these (except RAS/NF1) were mutually exclusive, suggesting that they each cause aberrant activation a common target. Expressing mutant molecules-but not their wild-type counterparts-rendered Ba/F3 cells independent IL3 by activating RAS-MEK-ERK PI3K-AKT pathways....
Background Deregulation of microRNA may contribute to hematopoietic malignancies. MicroRNA-196b (miR-196b) is highly expressed in MLL-rearranged leukemia and has been shown be activated by MLL MLL-fusion genes.Design Methods In order determine whether high expression miR-196b restricted leukemia, we used quantitative stem-loop reverse transcriptase polymerase chain reaction measure the this 72 selected cases pediatric acute lymphoblastic i.e. non-MLL-rearranged precursor B-cell T-cell...
Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early precursor immunophenotype or expression profile, MEF2C-dysregulated cluster based on gene analysis (immature cluster) and retain non-rearranged TRG@ loci. Early exclusively overlap with samples the of signature genes, indicating both are featuring a single disease entity. Patients lacking rearrangements represent only 40% cases, but no further evidence was found to...
Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved regulating RNA maturation translation. Combined silencing genes, but not either gene alone, accelerated leukemogeneis Tal1/Lmo1/Notch1-driven mouse model, demonstrating the...
Translocation of the LYL1 oncogene are rare in T-cell acute lymphoblastic leukemia, whereas homologous TAL1 gene is rearranged approximately 20% patients. Previous gene-expression studies have identified an immature leukemia subgroup with high expression absence chromosomal aberrations. Molecular characterization a t(7;19)(q34;p13) pediatric patient led to identification translocation between TRB@ and loci. Similar incidental cases synergistic, double translocations affecting TAL1/2 LMO1/2...
Abstract Leukemia is characterized by oncogenic lesions that result in a block of differentiation, whereas phenotypic plasticity retained. A better understanding how these two phenomena arise during leukemogenesis humans could help inform diagnosis and treatment strategies. Here, we leveraged the well-defined differentiation states T-cell development to pinpoint initiation acute lymphoblastic leukemia (T-ALL), an aggressive form childhood leukemia, study emergence plasticity. Single-cell...
Monoallelic inactivation of CCCTC-binding factor (CTCF) in human cancer drives altered methylated genomic states, CTCF occupancy at promoter and enhancer regions, deregulated global gene expression. In patients with T cell acute lymphoblastic leukemia (T-ALL), we find that acquired monoallelic CTCF-inactivating events drive subtle local effects nearly half t(5; 14) (q35; q32.2) rearranged patients, especially when CTCF-binding sites are preserved between the BCL11B TLX3 oncogene. These...
Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is urgent to recognize T-LBL through identification molecular characteristics biomarkers. By using RNA sequencing which was performed 29/49 were diagnosed the Princess Maxima...
The glucocorticoid receptor NR3C1 is essential for steroid-induced apoptosis, and deletions of this gene have been recurrently identified at disease relapse acute lymphoblastic leukemia (ALL) patients. Here, we demonstrate that recurrent inactivating aberrations—including deletions, missense, nonsense mutations—are in 7% pediatric T-cell ALL patients diagnosis. These aberrations are frequently present early thymic progenitor-ALL relate to steroid resistance. Functional modeling pre-B cell...
Physiological and pathogenic interleukin-7-receptor (IL7R)-induced signaling provokes glucocorticoid resistance in a subset of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Activation downstream STAT5 has been suggested to cause steroid through upregulation anti-apoptotic BCL2, one its target genes. Here we demonstrate that isolated various T-ALL cell models is insufficient raise cellular despite BCL2 BCL-XL. Upregulation BCLXL STAT5-activated cells requires...