Assuntos
Vacina BNT162/efeitos adversos , Células da Medula Óssea/patologia , COVID-19/imunologia , Linfócitos/patologia , Linfo-Histiocitose Hemofagocítica/etiologia , Idoso de 80 Anos ou mais , Anorexia/etiologia , Astenia/etiologia , Vacina BNT162/administração & dosagem , Medula Óssea/patologia , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19 , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Masculino , Prurido/etiologia , SARS-CoV-2/genética , SARS-CoV-2/imunologiaRESUMO
Familial aggregation of hematological malignancies has been reported highlighting inherited genetic predisposition. In this study, we targeted four candidate genes: JAK2 and RUNX1 genes assuring a prominent function in hematological process and CBL and NPM1 as proto-oncogenes. Their disruption was described in several sporadic hematological malignancies. The aim of this study is to determine whether JAK2, CBL, RUNX1, and NPM1 germline genes mutations are involved in familial hematological malignancies. Using direct sequencing, we analyzed JAK2 (exons 12 and 14); CBL (exons 7, 8 and 9); NPM1 (exon 12) and the entire RUNX1 in 88 independent families belonging to Tunisian and French populations. Twenty-one sporadic acute leukemias were included in this study. We reported a heterozygous intronic c.1641 + 6 T > C JAK2 variant (rs182123615) found in two independent familial cases diagnosed with gastric lymphoma and Hodgkin lymphoma. The in silico analysis suggested a potential impact on splicing, but the functional splicing minigene reporter assay on rs182123615 variant showed no aberrant transcripts. In one sporadic acute myeloblastic leukemia, we reported an insertion 846 in. TGTT in exon 12 of NPM1 gene that may impact the normal reading frame. The rs182123615 JAK2 variant was described in several contexts including myeloproliferative neoplasms and congenital erythrocytosis and was supposed to be pathogenic. Through this current study, we established the assessment of pathogenicity of rs182123615 and we classified it rather as rare polymorphism.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Análise Mutacional de DNA/métodos , Neoplasias Hematológicas/genética , Janus Quinase 2/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-cbl/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Variação Genética/genética , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Nucleofosmina , LinhagemRESUMO
The incidence of malignancies has increased in conjunction with epidemic of human immunodeficiency virus (HIV) disease and they are currently considered acquired immunodeficiency syndrome (AIDS)-defining conditions. Approximately 40% of all patients with AIDS have developed cancer during the course of HIV infections. Further, as survival has improved in HIV disease, the incidence of these malignancies has increased. The main malignancies noted are Kaposi's sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, rectal and anal cancer.