RESUMEN
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.
Asunto(s)
Proteínas Relacionadas con la Autofagia/genética , Cromosomas Humanos Par 14/genética , Hematopoyesis Clonal , Duplicación de Gen , Leucemia Mieloide Aguda/patología , Síndromes Mielodisplásicos/patología , Trastornos Mieloproliferativos/patología , Proteínas Represoras/genética , Proteínas de Transporte Vesicular/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , Susceptibilidad a Enfermedades , Femenino , Estudios de Seguimiento , Células Germinativas , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Mutación , Síndromes Mielodisplásicos/genética , Trastornos Mieloproliferativos/genética , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenAsunto(s)
Proteínas Relacionadas con la Autofagia/genética , Células Germinativas , Leucemia Mieloide Aguda , Proteínas Represoras/genética , Proteínas de Transporte Vesicular/genética , Humanos , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/genética , Prevalencia , Indias OccidentalesAsunto(s)
Neoplasias de la Médula Ósea/diagnóstico , Neoplasias de la Médula Ósea/secundario , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/secundario , Leucemia Mieloide Aguda/diagnóstico , Neoplasias de la Médula Ósea/patología , Carcinoma Neuroendocrino/patología , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
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.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Neoplasias Orbitales/diagnóstico , Neoplasias Orbitales/virología , Biopsia , Diagnóstico Diferencial , Ojo/patología , Ojo/virología , Resultado Fatal , Infecciones por HTLV-I/diagnóstico , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
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.
