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internet, cited, httpspubmedncbinlmnihgov, tet, dec, jan, mutations, lymphoproliferative, human, article, madrid, lymphoma, cells, immunol, autoimmune, cell, spain, patients, clinical, germline, mutation, syndrome, leukemia, blood, feb, maría, cancer, dna, regulatory, clin, apr, immunity, fas, med, university, hospital, lópeznevado, allende, tcell, immune, tcells, disorders, research, phenotype, luis, gene, myeloid, loss, sep, department,

Topics {✒️}

extranodal nk/t-cell lymphoma human t-cell lymphoma oscar cabrera-marante double-negative t-cells cd30+ t-cell lymphomas month download article/chapter chronic lymphoproliferative disorders t-cell lymphoma constitutional copy-number variants immune cell development chronic lymphoproliferation reyes arranz-sáez somatic fas mutation cecilia muñoz-calleja estela paz-artal & luis genome-wide profiling identifies tet2-mediated foxp3 demethylation somatic rhoa mutation ana cerdá-montagud epstein-barr virus jak3/stat3 oncogenic pathway related disorders tet-mediated epigenetic regulation t-cell lymphomas related subjects germline tet2 mutation immune dysregulation javier ortiz-martín ten-eleven-translocation ifn-α production /article/view/2333 autoimmune lymphoproliferative syndrome autoimmune lymphoproliferative syndrome chronic myelomonocytic leukemia monoallelic tet2 mutation primary immunodeficiency disorders human lymphoproliferative syndrome estela paz-artal lrba gene deletion de la rica marta lópez-nevado adaptive immune system maintain immune homeostasis cytokine gene expression dendritic cell differentiation follicular helper cells brentuximab vedotin + etoposide cell lymphoma t-lgl leukemia distinct effector subsets

Questions {❓}

• Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?

Schema {🗺️}

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         headline:Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy
         description:Somatic mutations in the ten-eleven translocation methylcytosine dioxygenase 2 gene (TET2) have been associated to hematologic malignancies. More recently, biallelic, and monoallelic germline mutations conferring susceptibility to lymphoid and myeloid cancer have been described. We report two unrelated autoimmune lymphoproliferative syndrome-like patients who presented with T-cell lymphoma associated with novel germline biallelic or monoallelic mutations in the TET2 gene. Both patients presented a history of chronic lymphoproliferation with lymphadenopathies and splenomegaly, cytopenias, and immune dysregulation. We identified the first compound heterozygous patient for TET2 mutations (P1) and the first ALPS-like patient with a monoallelic TET2 mutation (P2). P1 had the most severe form of autosomal recessive disease due to TET2 loss of function resulting in absent TET2 expression and profound increase in DNA methylation. Additionally, the immunophenotype showed some alterations in innate and adaptive immune system as inverted myeloid/plasmacytoid dendritic cells ratio, elevated terminally differentiated effector memory CD8 + T-cells re-expressing CD45RA, regulatory T-cells, and Th2 circulating follicular T-cells. Double-negative T-cells, vitamin B12, and IL-10 were elevated according to the ALPS-like suspicion. Interestingly, the healthy P1’s brother carried a TET2 mutation and presented some markers of immune dysregulation. P2 showed elevated vitamin B12, hypergammaglobulinemia, and decreased HDL levels. Therefore, novel molecular defects in TET2 confirm and expand both clinical and immunological phenotype, contributing to a better knowledge of the bridge between cancer and immunity.
         datePublished:2022-09-06T00:00:00Z
         dateModified:2022-09-06T00:00:00Z
         pageStart:165
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      headline:Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy
      description:Somatic mutations in the ten-eleven translocation methylcytosine dioxygenase 2 gene (TET2) have been associated to hematologic malignancies. More recently, biallelic, and monoallelic germline mutations conferring susceptibility to lymphoid and myeloid cancer have been described. We report two unrelated autoimmune lymphoproliferative syndrome-like patients who presented with T-cell lymphoma associated with novel germline biallelic or monoallelic mutations in the TET2 gene. Both patients presented a history of chronic lymphoproliferation with lymphadenopathies and splenomegaly, cytopenias, and immune dysregulation. We identified the first compound heterozygous patient for TET2 mutations (P1) and the first ALPS-like patient with a monoallelic TET2 mutation (P2). P1 had the most severe form of autosomal recessive disease due to TET2 loss of function resulting in absent TET2 expression and profound increase in DNA methylation. Additionally, the immunophenotype showed some alterations in innate and adaptive immune system as inverted myeloid/plasmacytoid dendritic cells ratio, elevated terminally differentiated effector memory CD8 + T-cells re-expressing CD45RA, regulatory T-cells, and Th2 circulating follicular T-cells. Double-negative T-cells, vitamin B12, and IL-10 were elevated according to the ALPS-like suspicion. Interestingly, the healthy P1’s brother carried a TET2 mutation and presented some markers of immune dysregulation. P2 showed elevated vitamin B12, hypergammaglobulinemia, and decreased HDL levels. Therefore, novel molecular defects in TET2 confirm and expand both clinical and immunological phenotype, contributing to a better knowledge of the bridge between cancer and immunity.
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      dateModified:2022-09-06T00:00:00Z
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      keywords:
         ALPS
         ALPS-like
         Immune dysregulation
         Germline mutation
         Lymphoma lymphoproliferation
         Malignancy
         Somatic mutation
         TET2
         Immunology
         Infectious Diseases
         Internal Medicine
         Medical Microbiology
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