RESUMEN
Phosphoglycerate kinase (PGK) is glycolytic enzyme critical in the creation of adenosine triphosphate. Mutations in the gene for this enzyme, PGK1, are associated with PGK deficiency, which is characterized by neurologic symptoms, nonhereditary spherocytic hemolytic anemia, and myopathy. We present a 20-year-old male with a novel c.461T>C (p.L154P) PGK1 mutation and clinical disease complicated by anemia and neurological symptoms. There is no recommended treatment for PGK deficiency. Because of our patient's advanced disease progression, we initiated serial blood transfusions and report significant subjective improvement in the patient's physical condition before his passing from PGK deficiency-related complications.
Asunto(s)
Transfusión Sanguínea , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/terapia , Fosfoglicerato Quinasa/deficiencia , Mutación Puntual , Adulto , Humanos , Masculino , Fosfoglicerato Quinasa/genéticaAsunto(s)
Neoplasias , Niño , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Oncología Médica , Cuidados Paliativos , Toma de DecisionesRESUMEN
Chimeric fusion genes are highly prevalent in childhood acute lymphoblastic leukemia (ALL) and are mostly prenatal, early genetic events in the evolutionary trajectory of this cancer. ETV6-RUNX1-positive ALL also has multiple ( approximately 6 per case) copy number alterations (CNAs) as revealed by genome-wide single-nucleotide polymorphism arrays. Recurrent CNAs are probably "driver" events contributing critically to clonal diversification and selection, but at diagnosis, their developmental timing is "buried" in the leukemia's covert natural history. This conundrum can be resolved with twin pairs. We identified and compared CNAs in 5 pairs of monozygotic twins with concordant ETV6-RUNX1-positive ALL and 1 pair discordant for ETV6-RUNX1 positive ALL. We compared, within each pair, CNAs classified as potential "driver" or "passenger" mutations based upon recurrency and, where known, gene function. An average of 5.1 (range 3-11) CNAs (excluding immunoglobulin/T-cell receptor alterations) were identified per case. All "driver" CNAs (total of 32) were distinct within each of the 5 twin pairs with concordant ALL. "Driver" CNAs in another twin with ALL were all absent in the shared ETV6-RUNX1-positive preleukemic clone of her healthy co-twin. These data place all "driver" CNAs secondary to the prenatal gene fusion event and most probably postnatal in the sequential, molecular pathogenesis of ALL.
Asunto(s)
Dosificación de Gen , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Gemelos Monocigóticos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Humanos , Masculino , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMEN
We propose an integrated structural approach to search potential aptamer molecules for targeting cancer receptor proteins. We used the outer cellular domain of the B-lymphocyte antigen, CD19, as the target for this study. First, using available protein-aptamer structures deposited in the protein data bank as resources, structural annotation was performed to seek the most probable binding aptamer and its potential initial configuration to the CD19 structure. Using this initial structure, molecular dynamics (MD) simulations were performed for adjustment of the aptamer-binding. During this process, we observed an "aptamer walking" mechanism of the binding of the single-stranded RNA-aptamer to CD19: the aptamer molecule gradually adjusts its configurations and shifts toward favorable binding positions. However, the target molecule CD19 maintained a relatively stable conformation during this process. The interface area between the RNA-aptamer and CD19 increased from less than 8 nm2 to over 12 nm2 during a 2-µs MD simulation. Using a stable binding pose as the starting structure, we manually mutated the RNA-aptamer to a DNA-aptamer and found that the interface area was further increased to over 16 nm2 , indicating a stronger affinity compared to the RNA-aptamer. The RNA- and DNA-aptamers and their stable binding-poses to the CD19 molecule may be used as templates in designing potential aptamer molecules that target the B-cell marker molecule CD19 with enhanced specificity and stability.
Asunto(s)
Antígenos CD19/genética , Aptámeros de Nucleótidos/genética , ADN/genética , Conformación Proteica/efectos de los fármacos , Antígenos CD19/efectos de los fármacos , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Sitios de Unión , ADN/ultraestructura , Humanos , Simulación de Dinámica Molecular , Unión Proteica/efectos de los fármacosRESUMEN
The occurrence of a tracheoesophageal fistula (TEF) in the setting of lymphoma has only rarely been reported in the world literature. Most cases reported were associated with radiation therapy vs. chemotherapy alone. This report presents one case illustrating the difficulty encountered managing a TEF that developed while undergoing chemotherapy for T-cell lymphoblastic lymphoma.
Asunto(s)
Neoplasias del Mediastino/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Fístula Traqueoesofágica/etiología , Niño , Humanos , MasculinoRESUMEN
A 13-year-old boy and a 16-year-old girl both presented with headaches and nausea after they were diagnosed with severe acquired aplastic anemia. Both patients had symptoms and signs consistent with the clinical syndrome of pseudotumor cerebri including headaches, nausea, papilledema, and elevated intracranial pressure. Both patients were treated with therapeutic lumbar puncture and acetazolamide, which relieved their symptoms. Acetazolamide dosage was given while the patients underwent an immunosuppressive regimen. We hypothesize that the pseudotumor cerebri in these two pediatric patients was the result of an increased production of cerebrospinal fluid in response to anemia and that the removal of fluid and treatment with acetazolamide appear to be helpful in such cases.
Asunto(s)
Acetazolamida/uso terapéutico , Anemia Aplásica/diagnóstico , Seudotumor Cerebral/etiología , Adolescente , Anemia Aplásica/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Encéfalo/patología , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Seudotumor Cerebral/diagnósticoRESUMEN
Metastatic rhabdoid tumor of the kidney (RTK) is a highly lethal malignancy; only one survivor with stage 4 disease has been reported. The authors reviewed the cases of two patients with metastatic RTK who had excellent responses to therapy. Both patients were treated with radiation therapy and alternating courses of ifosfamide, carboplatin, and etoposide (ICE) and vincristine, doxorubicin, and cyclophosphamide (VDC). The patients are without evidence of disease at 24 months and 12 months from the detection of metastasis. Alternating courses of ICE and VDC have activity against metastatic RTK. This combination of agents warrants prospective investigation in clinical trials.