ORCID Profile
0000-0002-0397-1086
Current Organisations
KU Leuven
,
University Hospitals Leuven
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Publisher: Cold Spring Harbor Laboratory
Date: 19-07-2018
DOI: 10.1101/372383
Abstract: This study aims to identify recurrent genetic alterations in relapsed or refractory (RR) natural-killer/T-cell lymphoma (NKTL) patients who have achieved complete response (CR) with programmed cell death 1 (PD-1) blockade therapy. Seven of the eleven patients treated with pembrolizumab achieved CR while the remaining four had progressive disease (PD). Using whole genome sequencing (WGS), we found recurrent clonal structural rearrangements (SR) of the PD-L1 gene in four of the seven (57%) CR patients’ pretreated tumors. These PD-L1 SRs consist of inter-chromosomal translocations, tandem duplication and micro-inversion that disrupted the suppressive function of PD-L1 3’UTR. Interestingly, recurrent JAK3 -activating (p.A573V) mutations were also validated in two CR patients’ tumors that did not harbor the PD-L1 SR. Importantly, these mutations were absent in the four PD cases. With immunohistochemistry (IHC), PD-L1 positivity could not discriminate patients who archived CR (range: 6%-100%) from patients who had PD (range: 35%-90%). PD-1 blockade with pembrolizumab is a potent strategy for RR NKTL patients and genomic screening could potentially accompany PD-L1 IHC positivity to better select patients for anti-PD-1 therapy.
Publisher: SAGE Publications
Date: 2016
Publisher: Proceedings of the National Academy of Sciences
Date: 21-01-2005
Abstract: γ-Secretase is the protease responsible for amyloid β peptide release and is needed for Notch, N-Cadherin, and possibly other signaling pathways. The protease complex consists of at least four subunits, i.e., Presenilin, Aph1, Pen2, and Nicastrin. Two different genes encode Aph1A and Aph1B in man. A duplication of Aph1B in rodents has given rise to a third gene, Aph1C . Different mixes of γ-secretase subunits assemble in at least four human and six rodent complexes but it is not known whether they have different activities in vivo . We report here the inactivation of the three Aph1 genes in mice. Aph1A –/– embryos show a lethal phenotype characterized by angiogenesis defects in the yolk sac, neuronal tube malformations, and mild somitogenesis defects. Aph1B –/– or C –/– or the combined Aph1BC –/– mice (which can be considered as a model for total Aph1B loss in human) survive into adulthood. However, Aph1BC –/– deficiency causes a mild but significant reduction in amyloid β percursor protein processing in selective regions of the adult brain. We conclude that the biochemical and physiological repercussions of genetically reducing γ-secretase activity via the different Aph1 components are quite ergent and tissue specific. Our work provides in vivo evidence for the concept that different γ-secretase complexes may exert different biological functions. In the context of Alzheimer's disease therapy, this implies the theoretical possibility that targeting specific γ-secretase subunit combinations could yield less toxic drugs than the currently available general inhibitors of γ-secretase activity.
Publisher: American Society of Hematology
Date: 15-09-2022
Abstract: Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
Publisher: Springer Science and Business Media LLC
Date: 10-2018
Publisher: Oxford University Press (OUP)
Date: 12-10-2012
DOI: 10.1093/HMG/DDS436
Publisher: Wiley
Date: 11-2019
DOI: 10.1002/AJUM.12177
Publisher: Springer Science and Business Media LLC
Date: 11-2018
DOI: 10.1007/S10875-018-0570-3
Abstract: The original version of this article unfortunately did not display the appropriate captions in the figure. The correct version is displayed below.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 03-08-2018
No related grants have been discovered for Thomas Tousseyn.