Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters

Lemonnier, François; Couronné, Lucile; Parrens, Marie; Jaı̈s, Jean-Philippe; Travert, Marion; Lamant, Laurence; Tournillac, Olivier; Rousset, Thérèse; Fabiani, Bettina; Cairns, Rob A.; Mak, Tak W.; Bastard, Christian; Bernard, Olivier A.; Leval, Laurence de; Gaulard, Philippe

doi:10.1182/blood-2012-02-408542

Cited by 415 publications

(383 citation statements)

References 25 publications

Supporting

Mentioning

339

Contrasting

Unclassified

Order By: Relevance

“…TET2 frameshift and nonsense mutations were frequently identified in AITL (~70%), PTCL-NOS (~60% in T FH cell marker expressing subtype), and CTCL (~10%) [75,96–98]. In AITL, IDH2 and TET2 mutations were detected in the same patients, which is not the case in myeloid malignancies [77].…”

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

“…In AITL, IDH2 and TET2 mutations were detected in the same patients, which is not the case in myeloid malignancies [77]. In AITL and PTCL-NOS, TET2 mutations were associated with a worse prognosis [96]. Tet2 -deficient mouse models elicit altered T-cell differentiation and can develop T-cell lymphoma with T FH -like features [99,100].…”

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

See 1 more Smart Citation

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools.

show abstract

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

show abstract

“…Les mutations de TET2 sont observées chez environ 60 à 70 % des patients [22][23][24][25][26][27] et 2 de ces mutations sont présentes dans presque la moitié des cas [22,23]. Elles sont réparties sur la totalité du gène et sont de nature inactivatrice (mutations des sites d'épissage, mutations non-sens, faux-sens dans des régions conservées dans l'évolution).…”

Section: Mutations Ponctuelles Observées Dans Les Laitunclassified

“…Les mutations de DNMT3A surviennent chez 20 à 30 % des patients et sont quasiment toujours associées aux mutations de TET2 [23][24][25]27]. IDH2 est muté au niveau du codon R172 chez 20 à 30 % des patients [22,25,28], et ces mutations sont souvent associées à celles de TET2 [22,23]. Les mutations d'IDH2 ont pour effet d'inhiber indirectement les oxydases dépendantes du 2-oxoglutarate et du fer, telles que les protéines de la famille TET [29].…”

Section: Mutations Ponctuelles Observées Dans Les Laitunclassified

“…L'analyse transcriptomique montre que la mutation RHOA G17V est associée à l'activation de voies de signalisation telles que MAPK/ERK, PI3K/AKT, KRAS, RAC1, ou encore la voie alternative d'activation de NFB [30,31]. D'un point de vue pronostique, les mutations de TET2 sont associées à une moins bonne survie sans progression [22], mais aucune des anomalies génétiques associées aux LAIT (TET2, DNMT3A, IDH2, RHOA G17V) n'a d'impact discernable sur la survie globale [22,23,25,31].…”

Section: Mutations Ponctuelles Observées Dans Les Laitunclassified

See 1 more Smart Citation

Aspects moléculaires des lymphomes T périphériques (1)

et al. 2015

Self Cite

View full text Add to dashboard Cite

Molecular Genetics of Myelodysplastic Syndromes

Bejar

Steensma

2012

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic disorders characterised clinically by inefficient haematopoiesis, cytopenias of the peripheral blood and a risk of progression to acute myeloid leukaemia (AML). Molecularly, MDS can be associated with a wide range of acquired chromosomal abnormalities, epigenetic alterations and single gene mutations. These abnormalities affect diverse molecular pathways including ribonucleic acid (RNA) splicing machinery, epigenetic modifiers, haematopoietic transcription factors, receptor tyrosine kinase signalling, cell cycle regulation and apoptosis. The particular combination of somatic genetic lesions in any given patient will influence how their disease is manifested, and together with individual background germline genotype may explain much of the clinical heterogeneity associated with MDS. Here, the common genetic abnormalities that underlie MDS and how these abnormalities influence the development and progression of these disorders have been reviewed. Key Concepts: MDS represent a collection of disorders marked by abnormal, inefficient haematopoiesis, cytopenias of the peripheral blood and a predisposition for progression to AML. Like other haematopoietic malignancies, MDS arise from the clonal expansion of a single, abnormal haematopoietic cell. The abnormal MDS cells that maintain the disease have the ability to self‐renew and clonally expand because they have a selective growth advantage compared to their normal counterparts. Impaired haematopoietic differentiation in MDS can lead to cytopenias or to the production of terminally differentiated cells with abnormal function. A combination of somatic genetic abnormalities (acquired changes to the deoxyribonucleic acid (DNA) coding sequence), epigenetic abnormalities (heritable changes in gene expression) and marrow microenvironmental abnormalities contribute to the development and progression of MDS. Approximately, 50% of MDS cells have a chromosomal abnormality detectable by routine metaphase karyotype analysis. More than 75% of patients have acquired mutations in one or more genes known to be recurrently altered in MDS. Recurrent mutations in MDS implicate several molecular pathways in the development and progression of disease including; altered RNA splicing mechanisms, epigenetic changes in DNA methylation and histone modifications, activation of growth factor signalling cascades, impaired differentiation and abnormal regulation of cell cycle and apoptosis. Acquired mutations in several MDS genes have prognostic significance that is independent of clinically based prognostic scoring systems. Chromosomal abnormalities and mutations in some genes can predict response to specific therapies used to treat patients with MDS.

show abstract

Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters

Abstract: Inactivating mutations of the

Cited by 415 publications

References 25 publications

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Aspects moléculaires des lymphomes T périphériques (1)

Molecular Genetics of Myelodysplastic Syndromes

Contact Info

Product

Resources

About