RT Journal Article
T1 Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy
A1 López-Nevado, Marta
A1 Paz Artal, Estela Natividad
A1 Allende Martínez, Luis Miguel
AB malignancies. More recently, biallelic, and monoallelic germline mutations conferring susceptibility to lymphoid and myeloid cancerhave been described. We report two unrelated autoimmune lymphoproliferative syndrome-like patients who presented with T-celllymphoma associated with novel germline biallelic or monoallelic mutations in the TET2 gene. Both patients presented a history ofchronic lymphoproliferation with lymphadenopathies and splenomegaly, cytopenias, and immune dysregulation. We identified thefirst 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 andprofound increase in DNA methylation. Additionally, the immunophenotype showed some alterations in innate and adaptive immunesystem as inverted myeloid/plasmacytoid dendritic cells ratio, elevated terminally differentiated effector memory CD8 + T-cellsre-expressing CD45RA, regulatory T-cells, and Th2 circulating follicular T-cells. Double-negative T-cells, vitamin B12, and IL-10were elevated according to the ALPS-like suspicion. Interestingly, the healthy P1’s brother carried a TET2 mutation and presentedsome 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 betterknowledge of the bridge between cancer and immunity.
SN 0271-9142
SN 1573-2592
YR 2022
FD 2022-09-06
LK https://hdl.handle.net/20.500.14352/114123
UL https://hdl.handle.net/20.500.14352/114123
LA eng
NO López-Nevado M, Ortiz-Martín J, Serrano C, Pérez-Saez MA, López-Lorenzo JL, Gil-Etayo FJ, Rodríguez-Frías E, Cabrera-Marante O, Morales-Pérez P, Rodríguez-Pinilla MS, Manso R, Salgado-Sánchez RN, Cerdá-Montagud A, Quesada-Espinosa JF, Gómez-Rodríguez MJ, Paz-Artal E, Muñoz-Calleja C, Arranz-Sáez R, Allende LM. Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy. J Clin Immunol. 2023 Jan;43(1):165-180. doi: 10.1007/s10875-022-01361-y. Epub 2022 Sep 6. PMID: 36066697.
DS Docta Complutense
RD 10 abr 2025