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1.
Cell Rep ; 42(4): 112307, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-36972173

RESUMEN

Animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Vaccines remain successful at limiting severe disease and death, but the potential for further coronavirus zoonosis motivates the search for pan-coronavirus vaccines. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of 12 sarbecovirus glycan shields. Of the 22 N-linked glycan attachment sites present on SARS-CoV-2, 15 are shared by all 12 sarbecoviruses. However, there are significant differences in the processing state at glycan sites in the N-terminal domain, such as N165. Conversely, glycosylation sites in the S2 domain are highly conserved and contain a low abundance of oligomannose-type glycans, suggesting a low glycan shield density. The S2 domain may therefore provide a more attractive target for immunogen design efforts aiming to generate a pan-coronavirus antibody response.


Asunto(s)
COVID-19 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Animales , SARS-CoV-2 , Glicosilación , Polisacáridos/química
2.
Neuropathology ; 43(4): 313-318, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36451532

RESUMEN

A 65-year-old woman with a resolved history of epilepsy due to a motor vehicle accident and hippocampal sclerosis presented with recurrent de novo seizures. Brain imaging demonstrated enhancement in the left parieto-occipital lobe. At histopathological examination, the lesion displayed a diffuse lymphoid infiltrate comprised of small atypical lymphocytes, plasmacytoid lymphocytes, and scattered plasma cells with amyloid deposition. Pathology workup demonstrated a monotypic B-cell phenotype of the lymphoid infiltrate, expressing lambda light chain restriction and plasmacytic differentiation without MYD88 mutations. The patient had no systemic evidence of lymphoma, plasma cell dyscrasia, or amyloidosis. A diagnosis of low-grade B-cell lymphoma of the central nervous system with plasmacytic differentiation and amyloid deposition was made.


Asunto(s)
Amiloidosis , Linfoma de Células B , Humanos , Encéfalo/patología , Diferenciación Celular
3.
J Natl Compr Canc Netw ; 20(11): 1267-1275, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36351334

RESUMEN

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Adolescente , Humanos , Niño , Linfoma de Células B Grandes Difuso/patología , Oncología Médica
4.
bioRxiv ; 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-36052375

RESUMEN

The animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the impact of SARS-CoV-2. Vaccines remain successful at limiting severe disease and death, however the continued emergence of SARS-CoV-2 variants, together with the potential for further coronavirus zoonosis, motivates the search for pan-coronavirus vaccines that induce broadly neutralizing antibodies. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of several sarbecovirus glycan shields. Many N-linked glycan attachment sites are shared by all sarbecoviruses, and the processing state of certain sites is highly conserved. However, there are significant differences in the processing state at several glycan sites that surround the receptor binding domain. Our studies reveal similarities and differences in the glycosylation of sarbecoviruses and show how subtle changes in the protein sequence can have pronounced impacts on the glycan shield.

5.
Cancer Genet ; 248-249: 39-48, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33065430

RESUMEN

Trisomy 3 has been previously reported in association with T-cell lymphomas and less commonly in different types of non-Hodgkin B-cell lymphomas. Trisomy 3 has also been reported in two cases of pediatric post-transplant lymphoproliferative disorder (PTLD). We present comprehensive clinicopathologic review of two pediatric patients with cardiac and liver/intestinal allografts that developed polymorphic PTLD characterized by trisomy 3. Both patients had Epstein-Barr virus (EBV) viremia and EBV was positive in tissue by EBER in situ hybridization. Using karyotype analysis and fluorescence in situ hybridization, we identified trisomy 3 in both patients. Both patients responded to treatment and are now free of the PTLD. Trisomy 3, an uncommon cytogenetic finding in pediatric polymorphic PTLD, may be a recurrent cytogenetic aberration if confirmed in a larger study of pediatric PTLDs. Further clinical follow up might help stratify significance of trisomy 3 as a prognostic factor.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 3/genética , Infecciones por Virus de Epstein-Barr/epidemiología , Trasplante de Corazón/efectos adversos , Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/etiología , Trisomía/patología , Adolescente , Cardiomiopatía Dilatada/cirugía , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Enfermedades Intestinales/cirugía , Intestinos/trasplante , Cariotipificación , Hepatopatías/cirugía , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/virología , Recurrencia , Trisomía/genética
6.
JCI Insight ; 52019 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-31085832

RESUMEN

Despite current immunosuppressive strategies, long-term lung transplant outcomes remain poor due to rapid allogenic responses. Using a stringent mouse model of allo-airway transplantation, we identify the CCR4-ligand axis as a central node driving secondary lymphoid tissue homing and activation of the allogeneic T cells that prevent long-term allograft survival. CCR4 deficiency on transplant recipient T cells diminishes allograft injury and when combined with CTLA4-Ig leads to an unprecedented long-term lung allograft accommodation. Thus, we identify CCR4-ligand interactions as a central mechanism driving allogeneic transplant rejection and suggest it as a potential target to enhance long-term lung transplant survival.


Asunto(s)
Rechazo de Injerto/inmunología , Trasplante de Pulmón/efectos adversos , Receptores CCR4/metabolismo , Linfocitos T/inmunología , Traslado Adoptivo , Aloinjertos/inmunología , Aloinjertos/patología , Animales , Modelos Animales de Enfermedad , Femenino , Rechazo de Injerto/patología , Supervivencia de Injerto/inmunología , Humanos , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Noqueados , Prueba de Estudio Conceptual , Receptores CCR4/genética , Receptores CCR4/inmunología , Transducción de Señal/genética , Transducción de Señal/inmunología , Linfocitos T/metabolismo , Linfocitos T/trasplante , Trasplante Homólogo/efectos adversos
7.
J Assoc Genet Technol ; 42(2): 60-3, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27584682

RESUMEN

The t(11;14)(q13;q32) involving IGH and CCND1 a nd t(9;22) (q34;q11.2) involving BCR and ABL1 are common abnormalities in plasma cell myeloma (PCM) and chronic myelogenous leukemia (CML), respectively. However, the concurrence of the two malignancies is extremely rare. Herein, we present a case of an 87-year-old male who presented with anemia and monocytosis. FISH studies on a bone marrow sample enriched for plasma cells detected a t(11;14) positive for IGH and CCND1 fusion in 92% of nuclei. However, cytogenetic analysis of the bone marrow revealed a t(9;22)(q34;q11.2) in 40% of the metaphases. Interphase and metaphase FISH studies on the sample confirmed the presence of the BCR-ABL1 fusion in 88% of nuclei but did not show any signals corresponding to the derivative 9, suggesting a variant t(9;22) with a deletion or additional material of unknown origin at the 9q34 band of the derivative 9 and a derivative 22 bearing the BCR-ABL1 fusion gene. The concurrence of plasma cell myeloma and chronic myelogenous leukemia is extremely rare with less than 20 cases reported. The molecular pathway in which the multiple malignancies arise is still poorly understood, and this case provides insight into the concurrence of PCM and CML.

8.
J Pediatr Hematol Oncol ; 38(6): 476-8, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27322719

RESUMEN

A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia.


Asunto(s)
Herpes Zóster/etiología , Reacción Leucemoide/etiología , Meningitis Viral/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicaciones , Crisis Blástica , Femenino , Herpes Zóster/líquido cefalorraquídeo , Humanos , Reacción Leucemoide/líquido cefalorraquídeo , Meningitis Viral/líquido cefalorraquídeo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Recurrencia , Adulto Joven
9.
Int J Clin Exp Med ; 7(3): 597-606, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24753753

RESUMEN

Aplastic anemia is a heterogeneous disorder of bone marrow failure syndrome. Accumulating evidence indicates that both acquired and congenital aplastic anemia is linked to telomerase activity and telomere length. Chinese herbal medicine Tianshengyuan-1 (TSY-1), a liquid extraction of multiple Chinese herbs, appears to stimulate hematopoiesis in patients with bone marrow deficiencies; however, the exact mechanism of action remains unclear. In this study, we investigated the effect of TSY-1 on telomere length and telomerase activity. We first investigated the effects of TSY on in vitro cultured cell lines including CD34+ hepatic stem cells and CD4+/CD8- Jurkat cells. An immune-mediated murine aplastic anemia model and human samples, including peripheral blood samples of 4 healthy donors and bone marrow hematopoietic cells from 4 patients with hypocellular myelodysplastic syndrome (MDS), were also used to test the efficacy of TSY on hematopoiesis, telomerase activity and telomere length. Our results indicated that TSY-1 increased the telomerase activity and telomere length in a dose-response manner in vitro, in vivo, and in human samples including 3 of 4 healthy individuals and 3 of 4 bone marrow samples from MDS patients. In immune-mediated murine aplastic anemia model, TSY-1 activity on Telomere length was parallel to the significant increasing of the RBC, hemoglobin, hematocrit, and platelet count in peripheral blood, increasing of CD34+ cell count and hematopoiesis, and decreasing of fatty infiltration in bone marrow samples. Our study demonstrated that TSY-1 may exert its effects by modulating telomerase activity of hematopoietic cells. Further studies are warranted to explore the precise molecular mechanisms of how TSY-1 regulates telomerase activity and telomere length, and also to test the TSY-1 in randomized control trials.

10.
Am J Clin Pathol ; 139(4): 466-90, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23525617

RESUMEN

Session 1 of the 2011 Workshop of the Society for Hematopathology and European Association for Haematopathology focused on mycosis fungoides (MF), the most common cutaneous lymphoma. The 62 cases in this case group demonstrated a wide spectrum of clinicopathologic features, including those seen in typical cases as well as those, by contrast, with atypical clinical history, morphology, immunophenotype, and/or genotype. Of the 62 cases, 27 (44%) were presented at the workshop and highlighted diagnostic challenges plus related issues. This report summarizes the approach recommended for making a confident diagnosis of MF and its clinically significant variants; emphasizes pitfalls in evaluating early MF, assessing nodal involvement, and diagnosing transformed MF; and discusses the relationship between MF and primary cutaneous CD30+ T-cell lymphoproliferative disorders. Last, Sézary syndrome is discussed, with concentration on those features distinct from MF.


Asunto(s)
Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Humanos
11.
Diagn Cytopathol ; 40(7): 635-8, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21381228

RESUMEN

Primary effusion lymphoma or body cavity based lymphoma is a form of large B-cell lymphoma which usually presents as serous effusions without detectable tumor masses. It is universally associated with human herpesvirus-8 also known as Kaposi sarcoma herpesvirus. This condition, so far, has been reported in the body cavity effusions that include pleura, peritoneum, and pericardium. We report a case of primary effusion lymphoma which has involved the cerebrospinal fluid. To our knowledge, this is the first case of PEL reported in the cerebrospinal fluid.


Asunto(s)
Infecciones por Herpesviridae/líquido cefalorraquídeo , Herpesvirus Humano 8/aislamiento & purificación , Linfoma de Efusión Primaria/líquido cefalorraquídeo , Núcleo Celular/patología , Forma de la Célula , Citoplasma/patología , VIH/patogenicidad , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/patogenicidad , Humanos , Inmunohistoquímica , Linfoma de Efusión Primaria/diagnóstico , Linfoma de Efusión Primaria/virología , Masculino , Persona de Mediana Edad
12.
Cytometry B Clin Cytom ; 80(2): 126-9, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21337493

RESUMEN

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a subtype of myelodysplastic/myeloproliferative neoplasm. Although several studies have reported concurrent myelodysplastic syndrome (MDS) and T-cell large granular lymphocytic leukemia (T-LGL), coexistence of CMML and T-LGL has not been characterized. We describe here a unique case of CMML plus an underlying T-LGL-type clonal proliferation in a patient with a long standing history of severe anemia and recent pancytopenia. METHODS: Multiparametric immunophenotyping by flow cytometry was conducted using fresh peripheral blood collected in EDTA. In addition, morphologic evaluation of the peripheral blood smear and T-cell gene rearrangement studies by polymerase chain reaction (PCR) were performed. RESULTS: Flow cytometric analysis revealed abnormal monocytosis with multiple aberrancies including expression of cross-lineage markers CD2 and CD56, plus reduced expression of multiple antigens. In addition, abnormal CD8+ T-cells were identified, demonstrating dim expression of CD5 and dim to complete loss of CD7. In correlation with clinical history and morphologic review, a diagnosis of CMML plus underlying abnormal CD8+ T-cell lymphoproliferation was made. The clonality of these abnormal T-cells was confirmed by T-cell gene rearrangement studies. CONCLUSIONS: We have identified a unique case of CMML in association with subclinical T-LGL, neither of which, alone, could fully explain the clinicopathologic features identified. Our findings suggest that the coexistence of these two entities may not be coincidental, and it is likely that they may share a common pathogenic pathway related to immune-dysregulation.


Asunto(s)
Citometría de Flujo/métodos , Leucemia Linfocítica Granular Grande/complicaciones , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/diagnóstico , Anciano , Proliferación Celular , Clonación Molecular , Humanos , Masculino
13.
PLoS One ; 5(6): e11354, 2010 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-20613873

RESUMEN

Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg) in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF) after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-), and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+) and CD103(-) and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+) Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+) Treg frequency and inversely with BOS. Higher frequencies of CCR7(+) CD3(+)CD4(+)CD25(hi)Foxp3(+)CD45RA(-) lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.


Asunto(s)
Bronquiolitis Obliterante/prevención & control , Antígenos Comunes de Leucocito/inmunología , Receptores CCR7/inmunología , Linfocitos T Reguladores/inmunología , Bronquiolitis Obliterante/inmunología , Líquido del Lavado Bronquioalveolar , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Rechazo de Injerto , Humanos , Inmunohistoquímica , Trasplante de Pulmón
15.
J Pediatr Hematol Oncol ; 32(2): e57-60, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20168246

RESUMEN

INTRODUCTION: Infant acute lymphoblastic leukemia (ALL) is considered a high-risk entity. Patients diagnosed in the first 3 months of life have especially high mortality. By morphology, infant ALL is classified as a lymphoid lineage leukemia; however, its physiologic behavior has brought many to consider it a pathologic hybrid between lymphoid leukemia and myeloid leukemias. As such, standard of care currently employs the use of chemotherapeutic agents used commonly in ALL protocols and agents typically reserved for the treatment of myelogenous lineage leukemias. The role of hematopoietic stem cell transplantation and graft-versus-leukemia effect in these patients has not been well studied. CASE PRESENTATION: An earlier healthy 9-week-old Hispanic male diagnosed with precursor B-cell lymphoblastic leukemia was treated with protocol P9407 and matched sibling hematopoietic stem cell transplantation. Relapse was noted on posttransplant day +114 with blasts on peripheral blood smear. The sole antigraft-versus-host disease (GVHD) agent, cyclosporine, was discontinued. Blast clearance from the peripheral blood was obtained by posttransplant day +128 with the appearance of skin and liver GVHD at posttransplant day +181. Bone marrow examination on posttransplant day +205 revealed normal marrow with no evidence of leukemic cells. He remains disease free more than 2 years posttransplant. CONCLUSION: Traditionally, graft-versus-leukemia effect was thought to contribute therapeutically little to the treatment of ALL by hematopoietic stem cell transplantation (HSCT). The effects of graft-versus-leukemia immunologic phenomenon in our patient with infant acute lymphoblastic leukemia underscore the potential that infant ALL may not be entirely the same biologic entity as standard pediatric ALL and may be more responsive than understood earlier. Therapeutic response and appearance of GVHD after the withdrawal of immunosuppression in this patient provides evidence that graft-versus-leukemia effect may play a role in disease control in infant ALL after HSCT. Patients who relapse after the HSCT may be salvaged with the withdrawal of immunosuppression. This suggests that other immunotherapeutic interventions in the context of relapse may offer potential clinical benefit in this disease.


Asunto(s)
Efecto Injerto vs Leucemia , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Humanos , Lactante , Masculino , Recurrencia , Trasplante Homólogo
16.
Arch Pathol Lab Med ; 132(6): 1021-5, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18517263

RESUMEN

Chronic myelogenous leukemia with blast crisis is seen in 15% to 20% of patients with chronic myelogenous leukemia. Chronic myelogenous leukemia with either erythroid or megakaryocytic blast crisis is not uncommon in the clinical setting. The incidence ranges from 0% to 33% in accordance with literature reports. The diagnosis of erythroid or megakaryocytic blast phase is often challenging because the percentage of blasts in the blood or bone marrow required for diagnosis has not been firmly established. Also, some myeloblasts can have aberrant expression of either erythroid or megakaryocytic markers by flow cytometry during clonal evolution. Early recognition of this entity is crucial because either megakaryocytic or erythroid blast crisis predicts an aggressive clinical course. To our knowledge, the coexistence of megakaryocytic and erythroid blasts has not been reported. We report a unique case of chronic myelogenous leukemia with this rare bilineage blast crisis in the background of dysplasia and marked myelofibrosis. Related literature is also reviewed.


Asunto(s)
Crisis Blástica/patología , Eritrocitos/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Megacariocitos/patología , Anciano , Antígenos CD/metabolismo , Antineoplásicos/uso terapéutico , Benzamidas , Resultado Fatal , Citometría de Flujo , Proteínas de Fusión bcr-abl , Humanos , Mesilato de Imatinib , Inmunofenotipificación , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Leuk Res ; 32(5): 823-7, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-17915315

RESUMEN

Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia rarely occur concurrently. We report a case in which these disorders were associated with an occult large granular lymphocyte leukemia. The peripheral blood cytopenias improved after glucocorticoids and intravenous immunoglobulin were administered, and response was maintained with cyclosporine. Large granular lymphocyte leukemia should be suspected in the setting of unexplained bone marrow failure.


Asunto(s)
Leucemia Linfocítica Granular Grande/complicaciones , Púrpura Trombocitopénica/complicaciones , Aplasia Pura de Células Rojas/complicaciones , Adulto , Antígenos CD/análisis , Femenino , Humanos , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/tratamiento farmacológico , Leucemia Linfocítica Granular Grande/inmunología , Receptores Inmunológicos/análisis , Familia de Moléculas Señalizadoras de la Activación Linfocitaria
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