RESUMO
We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.
Assuntos
Citopenia , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Neoplasias , Humanos , Síndromes Mielodisplásicas/genética , Mutação , Linfócitos T/patologia , Transtornos Mieloproliferativos/genéticaAssuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Linfoma Difuso de Grandes Células B , Segunda Neoplasia Primária , Adulto , Aloenxertos , Criança , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologiaRESUMO
Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.
Assuntos
Ferritinas/sangue , Sobrecarga de Ferro , Nefropatias , Hepatopatias , Síndrome Metabólica , Proteínas de Neoplasias/sangue , Neoplasias , Humanos , Inflamação/sangue , Inflamação/terapia , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/terapia , Nefropatias/sangue , Nefropatias/terapia , Hepatopatias/sangue , Hepatopatias/terapia , Síndrome Metabólica/sangue , Síndrome Metabólica/terapia , Neoplasias/sangue , Neoplasias/terapia , Guias de Prática Clínica como AssuntoAssuntos
Proteínas Mutadas de Ataxia Telangiectasia , Transformação Celular Neoplásica , Linfoma de Células B , Proteínas Proto-Oncogênicas c-myc , Proteína Supressora de Tumor p53 , Idoso , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoAssuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Epistaxe/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/complicações , Administração Intranasal , Aerossóis , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/economia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/economia , Bevacizumab , Cauterização , Terapia Combinada , Avaliação de Medicamentos , Epistaxe/etiologia , Epistaxe/cirurgia , Feminino , Humanos , Lasers de Corante/uso terapêutico , Masculino , Mucosa Nasal/efeitos dos fármacos , RecidivaRESUMO
Anaemia of chronic disease is the second most common form of anaemia worldwide, and is seen in a variety of inflammatory, infective and malignant diseases. Functional iron deficiency is fundamental to the pathogenesis of the anaemia, and the polypeptide, hepcidin, plays a key role. Diagnosis may be difficult, but new automated red cell indices, algorithms for detection of functional iron deficiency, and assays for hepcidin levels are being developed. Management of the causative disease process will usually improve haemoglobin levels, but where this is not possible, erythropoietic stimulating agents are often used, although there are still concerns about potential adverse effects, especially thromboembolism. There is increasing evidence that supplemental iron given parenterally can safely overcome the functional iron deficiency. Inhibitors of hepcidin, and various inflammatory modulators show promise for the future.
Assuntos
Anemia/diagnóstico , Algoritmos , Anemia/etiologia , Anemia/terapia , Peptídeos Catiônicos Antimicrobianos/antagonistas & inibidores , Peptídeos Catiônicos Antimicrobianos/fisiologia , Doença Crônica , Diagnóstico Diferencial , Eritropoetina/uso terapêutico , Hepcidinas , Humanos , Ferro/uso terapêuticoRESUMO
This study looked for clonal diversity in patients with a myeloproliferative neoplasm associated with more than one acquired genetic lesion. A tyrosine kinase mutation and a cytogenetic lesion were present in the same clone in six of seven patients. By contrast, the genetic lesions were present in separate clones in all six patients with two tyrosine kinase pathway mutations. Moreover, in two patients the clones were genetically unrelated by X-chromosome inactivation studies. These data demonstrated clonal diversity in a subset of patients with early stage haematopoietic malignancy and showed, for the first time, that such clones may arise independently.