RESUMO
ABSTRACT: Nonmelanoma skin cancers (NMSCs) in ruxolitinib-treated patients with myeloproliferative neoplasms behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis. Vigilant skin assessment, counseling on NMSC risks, and prospective ruxolitinib-NMSC studies are crucial.
Assuntos
Transtornos Mieloproliferativos , Pirazóis , Pirimidinas , Neoplasias Cutâneas , Humanos , Estudos Prospectivos , Transtornos Mieloproliferativos/tratamento farmacológico , Nitrilas , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
COVID-19/complicações , Transtornos Mieloproliferativos/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/terapia , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/terapia , SARS-CoV-2/isolamento & purificação , Análise de Sobrevida , Reino Unido/epidemiologiaRESUMO
Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.
Assuntos
Linfoma de Células T Associado a Enteropatia/fisiopatologia , Histona-Lisina N-Metiltransferase/fisiologia , Animais , Variações do Número de Cópias de DNA/genética , Linfoma de Células T Associado a Enteropatia/classificação , Linfoma de Células T Associado a Enteropatia/genética , Feminino , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Mutação/genética , Análise de Sequência de DNA , Linfócitos T/fisiologiaRESUMO
A 57-year-old man developed transient global amnesia within an hour of bolus unfractionated heparin administration on day 4 post-mitral valve replacement. Both immunoglobulin G-specific enzyme-linked immunosorbent assay and serotonin release assay were strongly positive for the antibodies that cause heparin-induced thrombocytopenia. The patient's cognitive functions returned to normal following discontinuation of unfractionated heparin and warfarin and commencement of lepirudin infusion.