RESUMO
The germline predisposition associated with the autosomal dominant inheritance of the 14q32 duplication implicating ATG2B/GSKIP genes is characterized by a wide clinical spectrum of myeloid neoplasms. We analyzed 12 asymptomatic carriers and 52 patients aged 18-74 years from six families, by targeted sequencing of 41 genes commonly mutated in myeloid malignancies. We found that 75% of healthy carriers displayed early clonal hematopoiesis mainly driven by TET2 mutations. Molecular landscapes of patients revealed two distinct routes of clonal expansion and leukemogenesis. The first route is characterized by the clonal dominance of myeloproliferative neoplasms (MPN)-driver events associated with TET2 mutations in half of cases and mutations affecting splicing and/or the RAS pathway in one-third of cases, leading to the early development of MPN, mostly essential thrombocythemia, with a high risk of transformation (50% after 10 years). The second route is distinguished by the absence of MPN-driver mutations and leads to AML without prior MPN. These patients mostly harbored a genomic landscape specific to acute myeloid leukemia secondary to myelodysplastic syndrome. An unexpected result was the total absence of DNMT3A mutations in this cohort. Our results suggest that the germline duplication constitutively mimics hematopoiesis aging by favoring TET2 clonal hematopoiesis.
Assuntos
Proteínas Relacionadas à Autofagia/genética , Cromossomos Humanos Par 14/genética , Hematopoiese Clonal , Duplicação Gênica , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/patologia , Transtornos Mieloproliferativos/patologia , Proteínas Repressoras/genética , Proteínas de Transporte Vesicular/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Suscetibilidade a Doenças , Feminino , Seguimentos , Células Germinativas , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/genética , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemAssuntos
Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Medula Óssea/secundário , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/secundário , Leucemia Mieloide Aguda/diagnóstico , Neoplasias da Medula Óssea/patologia , Carcinoma Neuroendócrino/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Adult T-cell Leukemia/Lymphoma (ATLL) is a sight- and life-threatening complication of human T-cell lymphotropic virus type 1 (HTLV-1) infection. Ophthalmic manifestations include uveitis, optic nerve oedema, retinal vasculitis, and lymphomatous infiltration. Orbital lesions are rare. We report the case of an orbital tumor revealing systemic ATLL in a 45-year-old Dominican patient who died despite treatment. Apart from late-grade cutaneous T-cell lymphoma, ATLL is the only T-lymphoma to develop in the orbit. Diagnosis is based on serologic evidence of HTLV-1 infection, cytology, and blood sample analysis. Biopsy is deemed necessary. Given the poor prognosis of ATLL and the worldwide presentation of HTLV-1, physicians should consider ATLL in the differential diagnosis of orbital malignant tumor and look for HTLV-1 infection in populations at risk.
Assuntos
Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Neoplasias Orbitárias/diagnóstico , Neoplasias Orbitárias/virologia , Biópsia , Diagnóstico Diferencial , Olho/patologia , Olho/virologia , Evolução Fatal , Infecções por HTLV-I/diagnóstico , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas.
