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See detailActivating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell–derived lymphomas
Vallois, David; Dobay, Maria Pamela D.; Morin, Ryan D. et al

in Blood (2016), 128

Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood ... [more ▼]

Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n 5 72) or other TFH-derived PTCL (n 5 13) by targeted deep sequencing of a gene panel enriched in T-cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays. Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%). Using in vitro assays in transfected cells, we demonstrated that 9 of 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from NFAT or NF-kB response element reporters, respectively. Collectively, the vast majority of variants in TCR-related genes could be classified as gain-of-function. Accordingly, the samples with mutations in TCR-related genes other than RHOA had transcriptomic profiles enriched in signatures reflecting higher T-cell activation. Although no correlationwithpresenting clinical featuresnor significantimpacton survivalwasobserved, thepresenceofTCR-relatedmutations correlated with early disease progression. Thus, targeting of TCR-related eventsmay hold promise for the treatment of TFH-derived lymphomas. [less ▲]

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See detailPrimary mucosa-associated lymphoid tissue lymphoma of the gallbladder: report of a case harboring API2/MALT1 gene fusion.
Bisig, Bettina ULg; Copie-Bergman, Christiane; Baia, Maryse et al

in Human Pathology (2009), 40(10), 1504-9

The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a ... [more ▼]

The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a case of mucosa-associated lymphoid tissue lymphoma of the gallbladder with genetic characterization. This lymphoma, diagnosed in a 75-year-old woman who underwent cholecystectomy for suspected acute cholecystitis, presented as diffuse thickening of the gallbladder wall. The morphology was typical of mucosa-associated lymphoid tissue lymphoma, and by immunophenotype, the tumor cells were CD20+ CD5- CD10- CD23- CD43- BCL6- BCL2+ IgM+ IgD- lambda+, with moderate nuclear expression of BCL10. Interphase fluorescence in situ hybridization analysis on paraffin sections, using a fusion probe for API2/MALT1, demonstrated 2 fusion signals in most nuclei, bringing the first documentation of a t(11;18)(q21;q21) in this exceptional primary disease location. [less ▲]

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See detailThe gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (T-FH) cells
de Leval, Laurence ULg; Rickman, David; Thielen, Caroline ULg et al

in Blood (2007), 109(11), 4952-4963

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ... [more ▼]

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T-FH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T-FH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T-FH genes was validated by immunohistochemistry in AITLs. A few cases with molecular T-FH-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that TFH cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL. [less ▲]

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See detailOutcome is not improved by the use of alternating chemotherapy in elderly patients with aggressive lymphoma
Bosly, André; Lepage, Eric; Coiffier, Bertrand et al

in Hematology Journal : The Official Journal of the European Haematology Association (2001), 2

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See detailPrognostic Significance of bcl-2 Protein Expression in Aggressive Non-Hodkin's Lymphoma
Hermine, Olivier; Haioun, Corinne; Lepage, Eric et al

in Blood (1996)

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