Long non-coding RNA (LncRNA) CHROMR promotes the expression of the CNNM1 gene by adsorbing hsa-miR-1299 to obtain drug resistance in diffuse large B lymphoma cells.

Background: Long non-coding RNA (LncRNA) play roles in different diseases, LncRNA is differentially expressed in diffuse large B cell lines with varying degrees of resistance to rituximab. Methods: In the GEO database (GSE159852), we found that CHROMR (cholesterol induced regulator of metabolism RNA) may be differentially expressed in different rituximab-resistant diffuse large B lymphoma cell lines. We also verified the expression level in cell lines and verified the role of CHROMR in acquiring cell drug resistance through various biological function experiments. We predict that there may be a potential regulatory mechanism for CHROMR and validated it. Results: We found that CHROMR was differentially expressed in different rituximab-resistant cell lines. When the rituximab-sensitive cell line SU_DHL_4 was stimulated by rituximab, flow experiments demonstrated that overexpression of CHROMR could reduce the level of cell apoptosis and the proportion of arrested cells in the G2/M phase of the cell cycle. cck8 experiments demonstrated that overexpression of CHROMR increased cell proliferation. Western Blot (WB) experiments confirmed that overexpression of CHROMR reduced the expression of apoptosis-related proteins. Dual-luciferase and recovery experiments suggested that CHROMR acted through the CHROMR/hsa-miR-1299/CNNM1 pathway. Conclusions: lncRNA CHROMR promotes the expression of the CNNM1 gene by adsorbing hsa-miR-1299 to obtain drug resistance in diffuse large B lymphoma cells.

Diagnostic Considerations in the Evaluation of Large B-Cells on Lymph Node Cytology Specimens.

Fine needle aspiration (FNA) has become increasingly popular in the evaluation of lymph nodes for lymphoproliferative disorders, but there are limitations to accurate subclassification of lymphoma using morphology alone. This case aims to expand diagnostic considerations of large B-cell populations identified on FNA material. We also address the significance of Epstein-Barr virus (EBV) DNA in the workup of patients with suspected lymphoma by FNA.

An epigenetic regulator-related score (EpiScore) predicts survival in patients with diffuse large B cell lymphoma and identifies patients who may benefit from epigenetic therapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma and shows considerable clinical and biological heterogeneity. Much research is currently focused on the identification of prognostic markers for more specific patients' risk stratification and on the development of therapeutic approaches to improve the long-term outcome. Epigenetic alterations are involved in various cancers, including lymphoma. Interestingly, epigenetic alterations are reversible and drugs to target some of them have been developed. In this study, we demonstrated that the gene expression profile of epigenetic regulators has a prognostic value in DLBCL and identified pathways that could be involved in DLBCL poor outcome. We then designed a new risk score (EpiScore) based on the gene expression level of the epigenetic regulators DNMT3A, DOT1L, SETD8. EpiScore was predictive of overall survival in DLBCL and allowed splitting patients with DLBCL from two independent cohorts (n = 414 and n = 69) in three groups (high, intermediate and low risk). EpiScore was an independent predictor of survival when compared with previously described prognostic factors, such as the International Prognostic Index (IPI), germinal center B cell and activated B cell molecular subgroups, gene expression-based risk score (GERS) and DNA repair score. Immunohistochemistry analysis of DNMT3A in 31 DLBCL samples showed that DNMT3A overexpression (>42% of positive tumor cells) correlated with reduced overall and event-free survival. Finally, an HDAC gene signature was significantly enriched in the DLBCL samples included in the EpiScore high-risk group. We conclude that EpiScore identifies high-risk patients with DLBCL who could benefit from epigenetic therapy.

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells.

BACKGROUND/AIMS: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. METHODS: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. RESULTS: Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. CONCLUSION: Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells.

Linfoma No-Hodgkin y pancreatitis aguda en gestante: reporte de caso / Non-Hodgkin's lymphoma and acute pancreatitis in pregnant women: case report

ANTECEDENTES: El linfoma no Hodgkin durante el embarazo es una entidad rara, el tipo difuso de células grandes es aún menos frecuente y se caracteriza por una alta tasa de progresión tumoral con poca expresión clínica. Su diagnóstico y tratamiento representan un reto clínico debido a la baja incidencia de la enfermedad y a las posibles repercusiones fetales a causa del tratamiento. CASO CLÍNICO: Gestante secundípara de 31 años que ingresa por cuadro de dolor abdominal y cifras elevadas de lactato deshidrogenasa. Durante la gestación precisa varios ingresos por pancreatitis aguda de repetición y cuadro de colestasis intrahepática. Tras el parto evoluciona tórpidamente con aparición de edema en esclavina en cuello y miembros superiores, siendo diagnosticada de gran masa torácica cuya biopsia es informada como Linfoma No Hodgkin tipo B difuso de células grandes primario mediastinal. Se administran dos ciclos de tratamiento quimioterápico tras lo cual remite completamente la enfermedad. Se induce el parto con prostaglandinas intravaginal, con recién nacido de 3350 gramos y APGAR 8/10. Tras un año la paciente permanece en remisión completa.

BACKGROUND: During pregnancy, Non-Hodgkin's lymphoma is a rare entity; the diffuse large cell lymphoma is still less common, and it has a high rate of tumor progression with a little clinical expression. Diagnosis and treatment is a huge challenge due to the low incidence of the condition and to the possible fetal effects because of the treatment. CLINICAL CASE: A 31-year-old woman -in her second delivery- was admitted with abdominal pain and elevated lactate dehydrogenase levels. During pregnancy, she was required several admissions reporting repeated acute pancreatitis and intrahepatic cholestasis. After delivery, it evolves into facial and upper extremity oedema, diagnosed with a large chest mass, resulting in the diagnosis of primary mediastinal large B-cell lymphoma through the biopsy. The disease goes into remission completely after two cycles of chemotherapy treatments are given. Labor is induced with intravaginal prostaglandins, with a newborn of 3350 g and Apgar 8/10. After a year, the patient remains in complete remission.

Síndrome icterico-obstructivo secundario a linfoma No Hodgkin de células B paracoledociano: a propósito de un caso / Obstructive jaundice syndrome secondary to paracoledocal non-hodgkin b cel lymphoma: a clinical case

Objetivo: Presentar la experiencia de un caso de Linfoma No Hodgkin paracoledociano con un cuadro de síndrome ictéricoobstructivo. Siendo una presentación poco frecuente. Caso Clínico: Paciente masculino de 50 años de edad, quien ingresa por un cuadro clínico compatible con síndrome ictérico-obstructivo de 2 meses de evolución, se le realiza ultrasonido abdominal, y tomografía abdomino-pélvica contrastada, con imágenes sugestivas de una probable lesión en la cabeza del páncreas y del proceso uncinado. Ante los hallazgos se indica ultrasonido endoscópico que concluye, una lesión por debajo de la confluencia esplenoportal e istmo pancreático hipoecogénica, de bordes definidos, de 27 x32 mm no relacionada ni con páncreas ni con hígado; se indica punción aspirado con aguja fina guiada por ultrasonido endoscópico, la cual reporta, fibrina, hemorragia e infiltrado por células redondas infl amatorias, nódulo fibroso, sin observar tumor. Se sugiere por lo tanto exploración quirúrgica para extraer tumor y drenaje de vía biliar. Se obtiene como hallazgos intraoperatorios, una lesión paracoledociana de bordes definidos, con estudio anatomopatológico e inmunohistoquímico compatible con Linfoma No Hodgkin de células B grandes. Paciente recibe quimioterapia en centro oncológico con evolución clínica satisfactoria. Discusión: El linfoma No Hodgkin de células B, es la forma mas común de presentación de linfoma y su presentación es variable, y se encuentra relacionado con la evidencia de adenopatías causantes de síntomas de tipo obstructivo por compresiones extrínsecas. El diagnóstico se basa en los estudios anatomopatológicos, por lo que se hace necesario la toma de un espécimen suficiente y su inclusión en estudios de inmunohistoquímica. El ultrasonido endoscópico se considera una herramienta diagnóstica de importancia ante las patologías hepatobiliares.

Objective: To present the experience of a case of non-Hodgkin lymphoma next to the common bile duct with a ictero-obstructive syndrome. Being a rare presentation. Case report: Male patient, 50 years old, who entered with a compatible clinical of an ictero-obstructive syndrome with two months of evolution, he performed abdominal ultrasound and a contrasted abdominalpelvic tomography with images suggestive of a probable injury in the head of the pancreas and the uncinate process. Because of this we indicate a Endoscopic ultrasound finding injury splenoportal below the isthmus junction and hypoechoic pancreatic of 27x32mm with defined edges, non-related to pancreas or liver; fine needle aspiration puncture guided by endoscopic ultrasound is indicated, which reports, fibrin, hemorrhage and infl ammatory infiltrated by round cells, fibrous nodule, without observing tumor. It is suggested therefore to extract tumor surgical exploration and biliary drainage. It is obtained as intraoperative findings, one injury defined borders, with Histopathological compatible with non-Hodgkin lymphoma of large B cells, next to the common bile duct. Patient receives chemotherapy in cancer center with good evolution. Discussion: Non-Hodgkins Lymphoma B cells, is the most common presentation of lymphoma, his presentation is variable, and is associated with evidence of lymphadenopathy causing obstructive symptoms by extrinsic compression. The diagnosis is based on pathological studies, so making a sufficient specimen and its inclusion in immunohistochemical studies are necessary. Endoscopic ultrasound is considered an important diagnostic tool to hepatobiliary diseases.

Características clínicas y resultados terapéuticos de linfomas no Hodgkin de células grandes B mediastinal primarios / Clinical features and therapeutic results of primary mediastinal large B- cells non-Hodgkin's lymphomas

Se realizó un estudio observacional, descriptivo y retrospectivo para evaluar las características clinicobiológicas y los resultados terapéuticos del linfoma de células grandes B mediastinal primario, en 34 pacientes atendidos en el Hospital Clinicoquirúrgico Hermanos Ameijeiras desde junio de 1989 a febrero de 2009. Se halló predominio del sexo femenino (61,8 por ciento), edad promedio de 31,5 años (19 a 61 años) y de la raza blanca (70,6 por ciento). Fueron más frecuentes los estadios localizados (67,7 por ciento), sin síntomas B (64,7 por ciento) y con gran masa tumoral (70,6 por ciento). La supervivencia global y la supervivencia libre de progresión a los 5 años fueron 53,4 y 43,4 por ciento, respectivamente. La supervivencia global a los 3 años de los pacientes tratados con MACOPB/VACOPB, CHOP y R-CHOP fue de 77,7; 30,4 y 100 por ciento, respectivamente. Se comprobó que los pacientes tratados con MACOPB/VACOPB tuvieron mejores resultados que los tratados con CHOP. El índice pronóstico internacional ajustado a la edad no fue predictor de supervivencia. En el análisis multivariable, el único predictor de supervivencia fue el tratamiento utilizado (CHOP contra MACOPB). El uso rutinario de la radioterapia no tuvo impacto significativo en la supervivencia global ni en la supervivencia libre de progresión a los 5 años(AU)

A retrospective, descriptive and observational study was conducted to assess the clinical-biological features and the therapeutic results of the primary mediastinal of large B cells lymphoma in 34 patients seen in the Hermanos Ameijeiras Clinical Surgical Hospital from June, 1989 to February, 2009. There was predominance of female sex (61.8 percent), mean age of 31.5 years (19 to 61 years) and of white race (70.6 percent). The localized stages were more frequent (67.7 percent), without B symptoms (64.7 percent) and with a large tumor mass (70.6 percent). Global survival and the free of progression survival at five years were of 53.4 and 43.4 percent, respectively. The global survival at three years of the patients treated with MACOPB/VACOPB, CHOP and R-CHOP was of 77.7; 30.4 and 100 percent, respectively. It was proved that patients treated with MACOPB/VACOPB had better results than those treated with CHOP. Age-adjusted international prognostic rate was not a survival predictor. In multivariable analysis, the only survival predictor was the applied (CHOP versus MACOPB). The routine use of radiotherapy has neither a significant impact on the global survival nor on the free of progression survival at five years(AU)

Características clínicas y resultados terapéuticos de linfomas no Hodgkin de células grandes B mediastinal primarios / Clinical features and therapeutic results of primary mediastinal large B- cells non-Hodgkin's lymphomas

Se realizó un estudio observacional, descriptivo y retrospectivo para evaluar las características clinicobiológicas y los resultados terapéuticos del linfoma de células grandes B mediastinal primario, en 34 pacientes atendidos en el Hospital Clinicoquirúrgico Hermanos Ameijeiras desde junio de 1989 a febrero de 2009. Se halló predominio del sexo femenino (61,8 por ciento), edad promedio de 31,5 años (19 a 61 años) y de la raza blanca (70,6 por ciento). Fueron más frecuentes los estadios localizados (67,7 por ciento), sin síntomas B (64,7 por ciento) y con gran masa tumoral (70,6 por ciento). La supervivencia global y la supervivencia libre de progresión a los 5 años fueron 53,4 y 43,4 por ciento, respectivamente. La supervivencia global a los 3 años de los pacientes tratados con MACOPB/VACOPB, CHOP y R-CHOP fue de 77,7; 30,4 y 100 por ciento, respectivamente. Se comprobó que los pacientes tratados con MACOPB/VACOPB tuvieron mejores resultados que los tratados con CHOP. El índice pronóstico internacional ajustado a la edad no fue predictor de supervivencia. En el análisis multivariable, el único predictor de supervivencia fue el tratamiento utilizado (CHOP contra MACOPB). El uso rutinario de la radioterapia no tuvo impacto significativo en la supervivencia global ni en la supervivencia libre de progresión a los 5 años

A retrospective, descriptive and observational study was conducted to assess the clinical-biological features and the therapeutic results of the primary mediastinal of large B cells lymphoma in 34 patients seen in the Hermanos Ameijeiras Clinical Surgical Hospital from June, 1989 to February, 2009. There was predominance of female sex (61.8 percent), mean age of 31.5 years (19 to 61 years) and of white race (70.6 percent). The localized stages were more frequent (67.7 percent), without B symptoms (64.7 percent) and with a large tumor mass (70.6 percent). Global survival and the free of progression survival at five years were of 53.4 and 43.4 percent, respectively. The global survival at three years of the patients treated with MACOPB/VACOPB, CHOP and R-CHOP was of 77.7; 30.4 and 100 percent, respectively. It was proved that patients treated with MACOPB/VACOPB had better results than those treated with CHOP. Age-adjusted international prognostic rate was not a survival predictor. In multivariable analysis, the only survival predictor was the applied (CHOP versus MACOPB). The routine use of radiotherapy has neither a significant impact on the global survival nor on the free of progression survival at five years