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1.
Pathol Int ; 71(1): 96-101, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33079423

RESUMEN

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed-Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5- , CD15+ , CD20- , CD30+ , PAX5+ , Bob.1- , Oct2- and EBER+ . The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein-Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection.


Asunto(s)
Linfoma de Células del Manto , Anciano , Autoinjertos/anomalías , Biomarcadores de Tumor/análisis , Ciclina D1/análisis , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hodgkin/patología , Humanos , Hibridación Fluorescente in Situ , Ganglios Linfáticos/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/patología , Masculino , Células de Reed-Sternberg/citología , Proteína p53 Supresora de Tumor/análisis
2.
PLoS Comput Biol ; 16(1): e1007516, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31961873

RESUMEN

In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significantly favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types.


Asunto(s)
Biología Computacional/métodos , Enfermedad de Hodgkin/patología , Interpretación de Imagen Asistida por Computador/métodos , Microambiente Tumoral/fisiología , Tamaño de la Célula , Enfermedad de Hodgkin/diagnóstico por imagen , Humanos , Inmunohistoquímica , Células de Reed-Sternberg/citología , Células de Reed-Sternberg/patología
3.
Lab Invest ; 97(7): 772-781, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28436953

RESUMEN

In classical Hodgkin's lymphoma (cHL), specific changes in the 3D telomere organization cause progression from mononuclear Hodgkin cells (H) to multinucleated Reed-Sternberg cells (RS). In a post-germinal center B-cell in vitro model, permanent latent membrane protein 1 (LMP1) expression, as observed in Epstein-Barr virus (EBV)-associated cHL, results in multinuclearity and complex chromosomal aberrations through downregulation of key element of the shelterin complex, the telomere repeat binding factor 2 (TRF2). Thus, we hypothesized that the three-dimensional (3D) telomere-TRF2 interaction was progressively disturbed during transition from H to RS cells. To this end, we developed and applied for the first time a combined quantitative 3D TRF2-telomere immune fluorescent in situ hybridization (3D TRF2/Telo-Q-FISH) technique to monolayers of primary H and RS cells, and adjacent benign internal control lymphocytes of lymph node biopsy suspensions from diagnostic lymph node biopsies of 14 patients with cHL. We show that H and RS cells are characterized by two distinct patterns of disruption of 3D telomere-TRF2 interaction. Disruption pattern A is defined by massive attrition of telomere signals and a considerable increase of TRF2 signals not associated with telomeres. This pattern is restricted to EBV-negative cHL. Disruption pattern B is defined by telomere de-protection due to an impressive loss of TRF2 signals, physically linked to telomeres. This pattern is typical of, but is not restricted to, LMP1+EBV-associated cHL. In the disruption pattern B group, so-called 'ghost' end-stage RS cells, void of both TRF2 and telomere signals, were identified, whether or not associated with EBV. Our findings demonstrate that two molecularly disparate mechanisms converge on the level of 3D telomere-TRF2 interaction in the formation of RS cells.


Asunto(s)
Enfermedad de Hodgkin/metabolismo , Células de Reed-Sternberg/metabolismo , Telómero/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células de Reed-Sternberg/citología , Telómero/química , Telómero/patología , Telómero/ultraestructura , Proteína 2 de Unión a Repeticiones Teloméricas/química , Adulto Joven
5.
Blood ; 124(19): 2897-8, 2014 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-25377557

RESUMEN

In this issue of Blood, Fhu et al report that Reed-Sternberg cell-derived lymphotoxin-α activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma (cHL), a process that is regulated by cyclooxygenase/nuclear factor-κB/activator protein 1 signaling pathways.


Asunto(s)
Linfocitos T CD4-Positivos/citología , Comunicación Celular/inmunología , Células Endoteliales/citología , Enfermedad de Hodgkin/metabolismo , Linfotoxina-alfa/metabolismo , Células de Reed-Sternberg/citología , Humanos
6.
Blood ; 124(19): 2973-82, 2014 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-25139349

RESUMEN

It is known that cells within the inflammatory background in classical Hodgkin lymphoma (cHL) provide signals essential for the continual survival of the neoplastic Hodgkin and Reed-Sternberg (HRS) cells. However, the mechanisms underlying the recruitment of this inflammatory infiltrate into the involved lymph nodes are less well understood. In this study, we show in vitro that HRS cells secrete lymphotoxin-α (LTα) which acts on endothelial cells to upregulate the expression of adhesion molecules that are important for T cell recruitment. LTα also enhances the expression of hyaluronan which preferentially contributes to the recruitment of CD4(+) CD45RA(+) naïve T cells under in vitro defined flow conditions. Enhanced expression of LTα in HRS cells and tissue stroma; and hyaluronan on endothelial cells are readily detected in involved lymph nodes from cHL patients. Our study also shows that although NF-κB and AP-1 are involved, the cyclooxygenase (COX) pathway is the dominant regulator of LTα production in HRS cells. Using pharmacological inhibitors, our data suggest that activity of COX1, but not of COX2, directly regulates the expression of nuclear c-Fos in HRS cells. Our findings suggest that HRS cell-derived LTα is an important mediator that contributes to T cell recruitment into lesional lymph nodes in cHL.


Asunto(s)
Linfocitos T CD4-Positivos/citología , Comunicación Celular/inmunología , Células Endoteliales/citología , Enfermedad de Hodgkin/metabolismo , Linfotoxina-alfa/metabolismo , Células de Reed-Sternberg/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Moléculas de Adhesión Celular/inmunología , Moléculas de Adhesión Celular/metabolismo , Línea Celular , Ciclooxigenasa 2/inmunología , Ciclooxigenasa 2/metabolismo , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Receptores de Hialuranos/inmunología , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/inmunología , Ácido Hialurónico/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Linfotoxina-alfa/inmunología , Células de Reed-Sternberg/inmunología , Células de Reed-Sternberg/metabolismo
7.
Blood ; 122(26): 4237-45, 2013 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-24136166

RESUMEN

The malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma are surrounded by a tumor microenvironment that is composed of a variety of cell types, as well as noncellular components such as collagen. Although HRS cells harbor oncogenic Epstein-Barr virus (EBV) in approximately 50% of cases, it is not known if the tumor microenvironment contributes to EBV-driven lymphomagenesis. We show that expression of the EBV-encoded latent membrane protein-1 (LMP1) in primary human germinal center B cells, the presumed progenitors of HRS cells, upregulates discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen. We also show that HRS cells intimately associated with collagen frequently overexpress DDR1 and that short-term exposure to collagen is sufficient to activate DDR1 in Hodgkin lymphoma-derived cell lines. The ectopic expression of DDR1 significantly increased the survival of collagen-treated DG75 Burkitt lymphoma cells, following etoposide treatment. Conversely, knockdown of DDR1 significantly decreased the survival of collagen-treated L428 Hodgkin lymphoma cells in the absence of specific apoptotic stimulus, suggesting that DDR1 also influences baseline survival. Our results identify a hitherto unknown function for collagen in protecting Hodgkin lymphoma cells from apoptosis and suggest an important contribution of the tumor microenvironment in promoting the oncogenic effects of EBV.


Asunto(s)
Linfocitos B/citología , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas de la Matriz Viral/genética , Linfocitos B/fisiología , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Muerte Celular/fisiología , Células Cultivadas , Colágeno/metabolismo , Receptor con Dominio Discoidina 1 , Infecciones por Virus de Epstein-Barr/patología , Regulación Viral de la Expresión Génica , Técnicas de Silenciamiento del Gen , Centro Germinal/citología , Enfermedad de Hodgkin/patología , Humanos , Fosforilación/fisiología , Proteínas Tirosina Quinasas Receptoras/genética , Células de Reed-Sternberg/citología , Células de Reed-Sternberg/fisiología , Microambiente Tumoral/fisiología
9.
Scand J Infect Dis ; 45(12): 953-6, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23848412

RESUMEN

The case of an HIV-positive man treated for acute toxoplasmosis with no traces of malignancy is reported. A second lymph node extirpation was performed after 5 months, which identified the presence of Hodgkin and Reed-Sternberg (HRS) cells. This case suggests that toxoplasmosis may cause changes in the regulation of surrounding cells and induce neoplastic proliferation.


Asunto(s)
Enfermedad de Hodgkin/parasitología , Toxoplasmosis/complicaciones , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/parasitología , Infecciones por VIH/patología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/virología , Humanos , Masculino , Células de Reed-Sternberg/citología , Toxoplasmosis/patología , Toxoplasmosis/virología
10.
Int J Cancer ; 131(4): E382-94, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22020966

RESUMEN

CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene. Our study was carried out to examine the role of CD99 in tumor progression of classical Hodgkin lymphoma (cHL). Here, we showed that lowly expressed CD99 protein in cHL cell lines and primary cHL cases correlates with the deficient expression of the positive regulatory domain 1 (PRDM1/BLIMP1). In addition, cHL cell lines showed high levels of miR-9 expression. We determined that the upregulation of CD99 induced expression of transcription factor PRDM1, a master regulator of plasma-cell differentiation, which is also a target for miR-9-mediated downregulation. Indeed, inhibition of miR-9 also triggered upregulation of PRDM1 expression. Furthermore, overexpression of CD99 resulted in changed growth features and reorganization of actin cytoskeleton. As upregulation of CD99 led to a decrease in cHL diagnosis marker CD30 and CD15 and an increase in plasma-cell differentiation marker CD38 and the restoration of B-cell makers PAX5, CD79α and CD19, we suggest that downregulated CD99 leads to the prevention of plasma-cell differentiation in Hodgkin/Reed-Sternberg (H/RS) cells. Furthermore, these data indicate that CD99 may control miR-9 expression, which directly targets PRDM1. Altogether, these results reveal a CD99-miR-9-PRDM1 molecule axis in lymphomagenesis of cHL and suggest that upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, which may provide a novel therapeutic strategies for cHL.


Asunto(s)
Antígenos CD/fisiología , Moléculas de Adhesión Celular/fisiología , Diferenciación Celular/fisiología , Enfermedad de Hodgkin/patología , MicroARNs/fisiología , Células de Reed-Sternberg/fisiología , Proteínas Represoras/fisiología , Regulación hacia Arriba/fisiología , Antígeno 12E7 , Secuencia de Bases , Western Blotting , Línea Celular Tumoral , Cartilla de ADN , Citometría de Flujo , Humanos , Separación Inmunomagnética , Hibridación in Situ , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Células de Reed-Sternberg/citología , Proteínas Represoras/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
11.
Mol Cell Biochem ; 321(1-2): 95-102, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18830569

RESUMEN

Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL) present an impaired expression of immunoglobulin genes, but escape apoptotic death. We investigated whether nitric oxide synthases (NOS) are expressed by H-RS cells, studied their association with EBV status and the expression of apoptotic proteins, and investigated their relationship to the clinical outcome of 171 patients. NOS1 and NOS2 were expressed in a large number of cases, whereas NOS3 expression was not detected. Positive associations were found between NOS1 and p53, bax and NOS2, bcl-2 and NOS2, bax and p53, and between bax and fasL. Inverse correlations were established between EBV and NOS2 and between EBV and bcl-2. A shorter overall survival (OS) was associated with strong expression of NOS2. In conclusion, NOS are expressed by H-RS cells of cHL.


Asunto(s)
Apoptosis/inmunología , Enfermedad de Hodgkin/inmunología , Isoenzimas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Células de Reed-Sternberg/enzimología , Células de Reed-Sternberg/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Enfermedad de Hodgkin/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Células de Reed-Sternberg/citología , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
12.
Blood ; 113(1): 108-16, 2009 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-18815281

RESUMEN

Expression of latent membrane protein 2 (LMP2A) during B-cell development leads to global alterations in gene transcription similar to those seen in Hodgkin Reed-Sternberg cells of Hodgkin lymphoma (HL). Along with the consistent detection of LMP2A in Epstein-Barr virus-associated HL, this implicates a role for LMP2A in the pathogenesis of HL. We have shown that LMP2A constitutively activates the Notch1 pathway to autoregulate the LMP2A promoter. To determine whether constitutive activation of the Notch pathway is important for LMP2A-mediated alterations in B-cell development in vivo, TgE-LMP2A-transgenic mice were intercrossed with mice expressing loxP-flanked Notch1 genes and Cre recombinase. B cells from TgE Notch1(lox/lox)-CD19(+/Cre) mice have an increase in immunoglobulin M and CD43 and a decrease in CD5 expression in the bone marrow compared with TgE Notch1(lox/lox) mice, indicating the LMP2A signal for developmental aberrations is impaired in the absence of Notch1. Real-time reverse-transcribed polymerase chain reaction analysis reveals that LMP2A requires the Notch1 pathway to alter levels of B cell-specific transcription factors, E2A and EBF. Interestingly, Notch1 appears to be important for LMP2A-mediated survival in low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells.


Asunto(s)
Linfocitos B/citología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Receptor Notch1/genética , Células de Reed-Sternberg/citología , Proteínas de la Matriz Viral/genética , Animales , Antígenos CD19/genética , Linfocitos B/inmunología , Linfocitos B/virología , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/virología , Supervivencia Celular/inmunología , Citometría de Flujo , Inmunoglobulina M/inmunología , Leucosialina/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptor Notch1/metabolismo , Células de Reed-Sternberg/inmunología , Células de Reed-Sternberg/virología , Transducción de Señal/inmunología , Bazo/citología
13.
Expert Rev Mol Diagn ; 7(6): 805-20, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18020910

RESUMEN

The microscopic pathology of Hodgkin lymphoma has been recognized for well over a century; however, only in the past 15 years has the enigmatic nature of this peculiar neoplasm been somewhat unraveled. This has been accomplished via a combination of the acquisition, via microdissection, of the prototypically rare malignant cells and their subsequent analysis via a variety of modalities, including genomic studies and expression profiling. This has facilitated the elucidation of the surreptitiously concealed B-cell origin of the cells, their complex but vital relationships with the surrounding micro- and macroenvironment, as well as multiple pathways involved in the pathobiology of this lymphoma. Understanding the intricacies of these intra- and extracellular pathways should allow for the development of less-toxic targeted therapies.


Asunto(s)
Enfermedad de Hodgkin , Células de Reed-Sternberg/fisiología , Herpesvirus Humano 4/inmunología , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/fisiopatología , Enfermedad de Hodgkin/terapia , Humanos , Tolerancia Inmunológica , Inflamación/inmunología , FN-kappa B/metabolismo , Fenotipo , Células de Reed-Sternberg/citología , Transducción de Señal/fisiología
14.
Leuk Lymphoma ; 48(10): 2042-53, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17917972

RESUMEN

To overcome some limitations of in vitro established cell-line tumor models for Hodgkin lymphoma (HL), we explored whether culturing in a three-dimensional (3D) matrix could improve the quality of the model. We used a novel designer peptide based self-organizing matrix. The gene expression profile of the 3D-cultured HL derived cell-line L1236 was compared with that of suspension-cultured (2D) L1236, as well as to the gene expression profile found in HL tumor samples. To validate our results we also included a gene expression data set of laser captured Hodgkin-Reed - Sternberg (H-RS) cells. The gene expression profiles were analyzed using Affymetrix technology. We found that the 3D culture affected gene expression of a HL derived cell-line inducing a more tumor-related expression profile. 3D culture affected the expression of 500 genes in L1236, upregulating genes involved in immune response and apoptosis and downregulating genes involved in cell division. It also affected genes involved in actin filament polymerization.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Enfermedad de Hodgkin/patología , Células de Reed-Sternberg/patología , Apoptosis , Biopsia , Línea Celular Tumoral , Biología Computacional , Humanos , Ganglios Linfáticos/patología , Modelos Genéticos , Análisis de Secuencia por Matrices de Oligonucleótidos , Péptidos/química , ARN Neoplásico/metabolismo , Células de Reed-Sternberg/citología
15.
Cancer Biol Ther ; 6(9): 1375-80, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17786031

RESUMEN

The Hodgkin-Reed-Sternberg (HRS) malignant cells in Hodgkin's lymphoma (HL) originate from germinal center B lymphocytes that did not undergo apoptosis. Protein Kinase C (PKC), a family of serine/threonine kinases, plays a crucial role in signal transduction modulating cell growth, differentiation and apoptosis. Here, we report the expression of PKC isoforms in two HL-derived cell lines, L428 and KMH2 and their correlation with drug resistance to CPT and doxorubicin. Among the PKC isoforms examined, only PKCeta and PKCbetaII were preferentially expressed in the drug resistant L428 cells. We have shown correlation between the response to apoptosis of L428 and KMH2 cells and PKCeta expression in these cell lines. In order to directly demonstrate a role for PKCeta in apoptosis, its expression was knocked-down by siRNA in the resistant L428 cells. Downregulation of PKCeta rendered L428 cells more sensitive to doxorubicin and CPT. Furthermore, PKCeta knocked-down cells showed increased PARP-1 cleavage, cytochrome c release and caspase 7 activation. It appears that PKCeta functions as an anti-apoptotic protein in HL-derived cell lines, and as we show here that it is also expressed in HRS of HL biopsies, it may have therapeutic relevance in HL. Thus, PKCeta could provide a new target aimed to reduce resistance to anti-cancer treatments of HL and other cancer patients.


Asunto(s)
Apoptosis , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Enfermedad de Hodgkin/metabolismo , Proteína Quinasa C/biosíntesis , Biopsia , Camptotecina/farmacología , Caspasa 7/metabolismo , Línea Celular Tumoral , Citocromos c/metabolismo , Doxorrubicina/farmacología , Activación Enzimática , Humanos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteína Quinasa C/química , Células de Reed-Sternberg/citología , Células de Reed-Sternberg/patología
16.
Immunobiology ; 210(1): 53-60, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16076034

RESUMEN

This adherence study was performed to clarify the trafficking of Hodgkin-Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) and thus try to unravel the peculiar pathways of dissemination in the early stages of this malignant neoplasm. Using non-neoplastic human necropsy or biopsy lymph node as well as tonsillar tissue sections, we have studied the adherence of the KMH-2 and L-428 HD-derived cell lines and have compared it to that of peripheral blood lymphocytes (PBLs). In necropsy lymph nodes, cell lines predominantly adhered to sinuses and paracortex, whilst adhered PBLs were distributed more widely. In biopsy lymph nodes, adhesion to high endothelial venules (HEVs) was rarely observed, whilst cell lines were found to adhere to sinuses. Inhibition by EDTA pretreatment affected adherence to HEVs as well as to sinuses and paracortex to a similar degree. Our findings point to the possible importance of the lymph node sinuses and paracortex in relation to homing of the HRS cells and their dissemination during the early stages of HD. The results suggest a significant primary role of the extracellular matrix of the paracortex and sinuses in the homing of HRS cells, with the HEVs of only secondary importance.


Asunto(s)
Enfermedad de Hodgkin/fisiopatología , Ganglios Linfáticos/citología , Células de Reed-Sternberg/citología , Biopsia , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Moléculas de Adhesión Celular , Línea Celular Tumoral , Ácido Edético/farmacología , Endotelio Linfático/citología , Matriz Extracelular/fisiología , Humanos , Ganglios Linfáticos/fisiopatología , Tonsila Palatina/citología
17.
MULTIMED ; 9(1)ene.-mar. 2005. CD-ROM
Artículo en Español | CUMED | ID: cum-35422

RESUMEN

Se presenta un caso de un paciente con clínica, ecografía y laparoscopia sugestivo deabsceso del músculo Psoas derecho. Por su evolución desfavorable y tras servalorado por un colectivo multidisciplinario se decide realizar la laparoscopia conposible diagnóstico de hernia atascada o quiste atascado en anillo inguinal profundo;en la intervención quirúrgica se obtiene una tumoración en FIO que se extrae yexamen histológico resultó ser un ganglio linfático por linfoma Hodgkin (AU)


Asunto(s)
Humanos , Masculino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin , Células de Reed-Sternberg/citología , Células de Reed-Sternberg , Diagnóstico por Imagen/métodos , Técnicas de Laboratorio Clínico
18.
Yale J Biol Med ; 78(4): 203-10, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16720015

RESUMEN

Classic Hodgkin's lymphoma is characterized by the appearance of giant abnormal cells called Hodgkin and Reed-Sternberg (HRS) cells. HRS cells arise from germinal center B lymphocytes and in about 50 percent of patients, are infected with Epstein-Barr Virus. In addition, HRS cells show constitutive NF-kappaB activation and are resistant to apoptosis. This paper reviews several recent studies that for the first time implicate specific molecules in the pathogenesis of classic Hodgkin's lymphoma. Targeting these molecules could lead to the development of novel therapies for this disease.


Asunto(s)
Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Animales , Apoptosis , Linfocitos B/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/virología , Humanos , FN-kappa B/metabolismo , Células de Reed-Sternberg/citología
19.
Zhonghua Xue Ye Xue Za Zhi ; 24(10): 510-4, 2003 Oct.
Artículo en Chino | MEDLINE | ID: mdl-14690578

RESUMEN

OBJECTIVE: To explore the origin and clonality of H/RS cells. METHODS: Immunohistochemical method was used to detect the expression of B-cell-specific activator protein (BSAP) and CD(20) in 33 paraffin-embedded tissues of classical Hodgkin lymphoma (cHL). IgH gene rearrangement was detected in 33 paraffin-embedded cHL tissue and 6 microsectioned H/RS cell samples. The PCR products of a case of cHL and its microsectioned cells were sequenced. RESULTS: H/RS cells were positive for BSAP in 30 of 33 (90.91%) cHL cases and positive for CD(20) in 10/33 (30.30%) cases. There was a significant difference between the expression of BSAP and CD(20) in H/RS cells (P = 0.000). BSAP and CD(20) were positive in almost all B cells of lymph node reactive hyperplasia and malignant cells in B-cell lymphomas while were negative in all malignant cells of T-cell lymphomas. 16 of 33 cHL were positive for gene rearrangement, and microsectioned H/RS cells in 14 of 19 tubes displayed clonal bands of rearrangement. There was no significant difference among the rearrangement rates in tubes containing different numbers of H/RS cells (P = 0.280). Sequencing analyses of the PCR products from both paraffin-embedded tissue and microsection of the same patient revealed the rearranged V segments, but the sequences were not identical. CONCLUSION: H/RS cells were originated from B cells of different differentiation stage.


Asunto(s)
Antígenos CD20/análisis , Proteínas de Unión al ADN/análisis , Reordenamiento Génico , Enfermedad de Hodgkin/patología , Cadenas Pesadas de Inmunoglobulina/genética , Células de Reed-Sternberg/citología , Factores de Transcripción/análisis , Adolescente , Adulto , Secuencia de Bases , Niño , Preescolar , Femenino , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/inmunología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Factor de Transcripción PAX5 , Análisis de Secuencia de ADN
20.
Adv Cancer Res ; 84: 277-312, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11883530

RESUMEN

Hodgkin's lymphoma (HL) is characterized by typical mononucleated Hodgkin and multinucleated Reed-Sternberg cells, which occur at low frequency in a mixed cellular infiltrate in the tumor tissue. Because of the rarity of these cells and their unusual immunophenotype, which is strikingly different from those of all normal hematopoietic cell types, the origin of these cells and their clonality have long been unclear. Single-cell studies of rearranged immunoglobulin genes showed that Hodgkin and Reed-Sternberg (HRS) cells represent clonal tumor-cell populations derived from germinal center B cells. In classical HL, the detection of obviously crippling immunoglobulin gene mutations in a fraction of the cases suggests that HRS cells may derive from germinal center B cells that have lost the capacity to be positively selected by antigen and that normally would have undergone apoptosis. In rare cases, HRS cells represent transformed T lymphocytes. The transforming events involved in malignant transformation of HRS cells are still largely unknown. Constitutive activation of the transcription factor NFkappaB, which can, for example, be induced through Epstein-Barr virus transformation of HRS cells or destructive somatic mutations of the inhibitor of NFkappaB, is likely to be a key event in HL pathogenesis. Significant progress has been made in our understanding of the cellular interactions in HL tissues, which are mainly mediated by a large variety of cytokines and chemokines.


Asunto(s)
Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/metabolismo , Células Presentadoras de Antígenos , Apoptosis , Aberraciones Cromosómicas , Genes Supresores de Tumor , Inmunofenotipificación , Modelos Biológicos , Mutación , Fenotipo , Células de Reed-Sternberg/citología
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