A5102955323- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Eosinophilic Disorders and Syndromes
- T-cell and Retrovirus Studies
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Gastrointestinal Tumor Research and Treatment
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Protein Tyrosine Phosphatases
- CAR-T cell therapy research
- Genetics and Neurodevelopmental Disorders
- Nuclear Structure and Function
- Neurofibromatosis and Schwannoma Cases
- Gastric Cancer Management and Outcomes
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- CRISPR and Genetic Engineering
- Platelet Disorders and Treatments
- Sarcoma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
VIB-KU Leuven Center for Cancer Biology
2012-2025
KU Leuven
2011-2025
Universitair Ziekenhuis Leuven
2006-2022
Center for Human Genetics
2006-2022
Cancer Institute (WIA)
2022
Wellcome Sanger Institute
2019
Cancer Genetics (United States)
2019
Vlaams Instituut voor Biotechnologie
2001-2014
VIB-KU Leuven Center for Microbiology
2014
Universidad de Navarra
2002-2007
Abstract ALK‐positive anaplastic large‐cell lymphoma (ALCL) has been recognized as a distinct type of in the heterogeneous group T/Null‐ALCL. While most ALCL (ALKomas) are characterized by presence NPM‐ALK fusion protein, product t(2;5)(p23;q35), 10–20% ALKomas contain variant ALK fusions, including ATIC‐ALK, TFG‐ALK, CLTC‐ALK (previously designated CLTCL‐ALK), TMP3‐ALK, and MSN‐ALK. TMP3‐ALK TMP4‐ALK fusions also have detected inflammatory myofibroblastic tumors (IMTs), making clear that...
Abstract Purpose: The majority of gastrointestinal stromal tumors harbor mutations in the receptor tyrosine kinases KIT or platelet-derived growth factor A (PDGFRA), and respond to treatment with kinase inhibitor imatinib. Some tumors, however, show primary resistance imatinib treatment, most others become resistant during treatment. common mechanism involves specific domains PDGFRA. We tested activity SU11248, an orally active small-molecule inhibitor, inhibit important imatinib-resistant...
RNA-seq is a promising technology to re-sequence protein coding genes for the identification of single nucleotide variants (SNV), while simultaneously obtaining information on structural variations and gene expression perturbations. We asked whether suitable detection driver mutations in T-cell acute lymphoblastic leukemia (T-ALL). These leukemias are caused by combination fusions, over-expression transcription factors cooperative point oncogenes tumor suppressor genes. analyzed 31 T-ALL...
Abstract Mutations in the receptor tyrosine kinase FLT3 occur frequently patients with acute myeloid leukemia (AML) and lymphoblastic (ALL). Small molecules that selectively inhibit activity induce apoptosis blasts from AML mutations prolong survival animal models of FLT3-induced myeloproliferative disease. A spectrum structurally different small against have been described, their efficacy for treatment ALL is now being investigated clinical trials. Here, we describe results an vitro screen...
Genetic abnormalities that result in expression of chimeric tyrosine kinase proteins such as BCR-ABL1 and ETV6-PDGFRβ are common causes hematopoietic malignancies. The paradigm for constitutive activation these fusion kinases is enforced homodimerization by self-association domains present the partner proteins. unique interstitial deletion on chromosome 4q12 leads to FIP1L1-PDGFRα was recently identified a cause chronic eosinophilic leukemia. In this report, we demonstrate FIP1L1 completely...
Background and Objectives Activated tyrosine kinases are implicated in the pathogenesis of chronic acute leukemia, represent attractive targets for therapy. Sorafenib (BAY43-9006, Nexavar®) is a small molecule B-RAF inhibitor that used treatment renal cell carcinoma, has been shown to have activity against receptor from platelet-derived growth factor (PDGFR) vascular endothelial (VEGFR) families. We investigated efficacy sorafenib at inhibiting mutants PDGFRβ, KIT, FLT3, which myeloid...
Activating NOTCH1 mutations are common in T-cell acute lymphoblastic leukemia. Inhibition of signaling with gamma-secretase inhibitors causes cell cycle block, but only after treatment for several days. We further documented the effects inhibitor on leukemia lines and tested whether combining other anti-cancer drugs offers a therapeutic advantage.The effect combinations chemotherapy or glucocorticoids was assessed lines. sequenced cases ABL1 fusions imatinib line.gamma-secretase 5-7 days...
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding the genetic landscape biology PTCL-NOS, we perform RNA-sequencing 18 cases validate results in an independent cohort 37 cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK SIN3A-FOXO1 new in-frame fusion transcripts, FYN-TRAF3IP2 recurrent detected 8 55...
The NUP214-ABL1 fusion protein is a constitutively active tyrosine kinase that found in 6% of patients with T-cell acute lymphoblastic leukemia and promotes proliferation survival T-lymphoblasts. Although sensitive to ABL1 inhibitors, development resistance these compounds major clinical problem, underlining the need for additional drug targets sparsely studied signaling network. In this work, we identify validate SRC family LCK as whose activity absolutely required cells depend on activity....
Translocations involving region 5q31-32 (PDGFRB) have been reported in a variety of myeloproliferative diseases and are often associated with significant peripheral eosinophilia. We report an unusual case patient presenting basophilia systemic mastocytosis whom cytogenetic analysis revealed t(4;5)(q21.1;q31.3).We used molecular analyses to determine the role PDGFRB this case. The was treated imatinib.Fluorescence situ hybridization (FISH) documented breakpoint PDGFRB. In agreement this,...
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell is characterized by 2p23/ALK aberrations, including the classic t(2;5)(p23;q35)/NPM1-ALK rearrangement present in ~80% of cases and several variant t(2p23/ALK) occurring remaining cases. The ALK fusion partners play a key role constitutive activation chimeric protein its subcellular localization. Using various molecular technologies, we have fusions eight recently diagnosed with cytoplasmic-only expression. identified partner...