Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center

Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

The Expression and Function of NK Cells in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the expression characteristics of antigens and functional markers of natural killer (NK) cells in patients with acute myeloid leukemia (AML).@*METHODS@#Multi-parameter flow cytometry was used to detect NK cell surface markers and their functional indicators in 56 newly diagnosed AML patients and 24 healthy controls, including activating receptors NKG2D, NKP46, DNAM-1, and killing indicators granzyme B, perforin.@*RESULTS@#Referring to the WHO hematopoiesis and lymph tissue tumor classification criteria, 56 cases were roughly divided into three types: AML M1, M2, and M4/M5. However, there was no differences about NK cells among the three types, so it was no longer subdivided. NK cells were divided into two groups: CD3-CD56hiCD16- (CD56hiNK) and CD3-CD56dimCD16+ (CD56dimNK). Compared with CD56dimNK cell population, except for NKP46, the positive expression levels of NKG2D and other receptors of CD56hiNK cells in AML patients decreased (P<0.001). Compared with healthy controls, the proportion of CD56hiNK cells in AML patients increased, while the number and proportion of NK cells and proportion of CD56dimNK cells significantly decreased (P<0.05). The proportion of perforin in CD56hiNK cells significantly increased (P<0.05). The expression of DNAM-1 in CD56hiNK cells, NKG2D, DNAM-1, and perforin in CD56dimNK cells decreased significantly (P<0.05). There was no statistically significant difference in expression of other functional indexes in AML patients compared with corresponding indexes of healthy controls. In addition, the proportion of CD56hiNK cells was positively correlated with the expression of CD34+ in AML (r=0.303).@*CONCLUSION@#Compared with CD56dimNK, the ratio of CD56hiNK and the expression of functional markers in AML patients are lower. Compared with healthy controls, the number and expression ratio of NK cells in AML patients decrease and the expression of functional markers is abnormal, indicating that its function is impaired.

Prognostic Significance of CD27 and CD56 on Newly Diagnosed MM Patients Treated with Bortezomib / 中国实验血液学杂志

OBJECTIVE@#To investigate the significance of CD27 and CD56 in the prognosis of multiple myeloma (MM) patients, and to establish a simple and convenient prognostic risk score.@*METHODS@#One hundred and eleven newly diagnosed MM patients treated by bortezomib in Shengjing hospital from January 1, 2013 to January 1, 2019 were selected, and the relationship between clinical characteristics and survival time of patients was analyzed.@*RESULTS@#The overall survival (OS) of patients in CD27@*CONCLUSION@#Among patients with MM treated by bortezomib, CD27

Expression of CD56 in Multiple Myeloma Cells and Its Relationship with Extramedullary Disease and Extramedullary Relapse / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD56 in multiple myeloma (MM) cells and its relationship between extramedullary disease and extramedullary relapse.@*METHODS@#Clinical data of 99 patients with MM treated in our hospital from January 2015 to December 2019 was retrospectively analyzed. The patients were divided into positive group and negative group according to the expression of CD56. The relationship between CD56 and multiple myeloma extramedullary disease, extramedullary relapse was analyzed.@*RESULTS@#Among 99 newly diagnosed patients with MM, the positive rate of CD56 was 65%, and the incidence of extramedullary disease of patients in the CD56 positive group was lower than that in the CD56 negative group (17.19% vs 48.57%) (P<0.01). Meanwhile, the incidence of extramedullary relapse of patients in the CD56 positive group was lower than that in the CD56 negative group (1.56% vs 34.29%) (P<0.01).@*CONCLUSION@#CD56 is highly expressed in MM, and its low expression is associated with the occurrence of extramedullary disease and extramedullary relapse, which suggests that CD56 may be an important indicator for predicting the occurrence of extramedullary disease and extramedullary relapse.

Reconstitución de células natural killer después del trasplante de células progenitoras hematopoyéticas en niños / Natural killer cell reconstitution after hematopoietic stem-cell transplantation in children

Resumen Introducción: Después de un trasplante de células progenitoras hematopoyéticas (TCPH), la reconstitución de las células natural killer (NK) es la principal barrera contra las infecciones virales. Objetivo: Determinar que el conocimiento sobre la cinética de la reconstitución de las células NK posterior al TCPH contribuye a un eficiente monitoreo del trasplante, lo que incrementa la posibilidad de éxito de este. Método: Se incluyeron 21 pacientes sometidos a TCPH, así como un grupo control de individuos clínicamente sanos. En diferentes momentos después del trasplante (intervalo de 21 a 670 días), mediante citometría de flujo se cuantificaron las células NK CD3− CD16+ CD56+ en muestras de sangre periférica. Resultados: La recuperación de las células NK ocurre entre los tres y seis meses y entre los 10 y 12 meses postrasplante; su número fue significativamente menor (en comparación con el grupo control) en el tiempo restante del monitoreo. Conclusiones: El primer periodo de recuperación de las células NK ocurre entre los tres y seis meses posteriores al trasplante. La reconstitución es transitoria y el número de células NK varía en los primeros años.

Abstract Introduction: After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cells reconstitution is the main barrier against viral infections. Objective: To determine that the knowledge on the kinetics of NK cell reconstitution after HSCT contributes to transplant efficient monitoring, which increases the possibility of its success. Method: Twenty-one patients undergoing HSCT were included, as well as a control group of clinically healthy individuals. At different time points after transplantation (range of 21 to 670 days), CD3- CD16+ CD56+ NK cells were quantified by flow cytometry in peripheral blood samples. Results: NK cell recovery occurs at three to six months and 10 to 12 months post-transplantation; their number was significantly lower (in comparison with the control group) in the rest of the monitoring time. Conclusions: The first period of NK cell recovery occurs between three and six months after transplantation. Reconstitution is transient and the number of NK cells varies in the first years.

Expression and significance of CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56, Syn and CgA in biopsy specimen of squamous cell carcinoma, adenocarcinoma and small cell lung carcinoma / Expresión y significado de CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56 Syn y CgA en muestras de biopsia de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas de pulmón

Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %,and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P<0.05), The incidences of a positive P40 expression were 100 % in squamous cell carcinoma, with specificity of 98.81 %.CK7, TTF-1 and NapsinA expression were more frequent in adenocarcinoma, with sensitivity and specificity of 85.09 % and 78.69 %, 79.82 % and 93.44 %, 56.14 % and 95.08 %, and compared with squamous cell carcinoma and small cell carcinoma difference was statistically significant (P<0.05). TTF-1, Syn, CgA and CD56 expression were more frequent in adenocarcinoma, with sensitivity and specificity of 86.33 % and 93.44 %, 89.21 % and 98.36 %, 74.10 % and 100 %, 96.40 % and 96.72 %. The combined detection of CK5/6, P63 and P40 were more useful and specific in differentiating squamous cell carcinoma. CK7, TTF-1 and NapsinA were more useful and specific in differentiating lung adenocarcinoma. The impaired CD56, TTF-1, Syn and CgA reflects the progression of small cell lung cancer.

Se midieron tumores y utilizaron nueve biomarcadores potenciales y se analizó la información para diagnosticar la enfermedad. A todos los pacientes se les realizó citología en líquido con broncoscopía de fibra y examen histopatológico para detectar de manera confiable el cáncer pulmonar. Se obtuvieron muestras de 314 pacientes chinos con cáncer de pulmón y CK5 / 6, P63, P40, CK7, TTF-1, Napsina A, CD56, Syn y CgA se midieron a través de histoquímica SP y analizaron la correlación de la expresión de estos marcadores con características patológicas y clínicas de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas en el cáncer de pulmón. El carcinoma de células escamosas, el adenocarcinoma y el carcinoma de células pequeñas fueron 61 casos, 114 casos y 139 casos, respectivamente, la expresión de CK5 / 6 y P63 fueron más frecuentes en el carcinoma de células escamosas, con una sensibilidad y especificidad del 77,05 % y 96,44 %, 83,61 % y 88,93 %, y en comparación con el adenocarcinoma y el carcinoma de células pequeñas, la diferencia fue estadísticamente significativa (P <0,05). La incidencia de ap la expresión positiva P40 fue del 100 % en el carcinoma de células escamosas, con una especificidad del 98,81 %. La expresión de CK7, TTF-1 y NapsinA fueron más frecuentes en el adenocarcinoma, con una sensibilidad y especificidad del 85,09 % y 78,69 %, 79,82 % y 93,44 %, 56,14 % y 95,08 %, y en comparación con el carcinoma de células escamosas y la diferencia de carcinoma de células pequeñas fue estadísticamente significativa (P <0,05) .TTF-1, Syn, CgA y la expresión de CD56 fueron más frecuentes en adenocarcinoma, con sensibilidad y especificidad de 86.33 % y 93.44 %, 89.21 % y 98.36 %, 74.10 % y 100 %, 96.40 % y 96.72 %. La detección combinada de CK5 / 6, P63 y P40 fue más útil y específica en la diferenciación del carcinoma de células escamosas. CK7, TTF-1 y NapsinA fueron más útiles y específicos para diferenciar el adenocarcinoma de pulmón. El deterioro de CD56, TTF-1, Syn y CgA refleja la progresión del cáncer de pulmón de células pequeñas.

Expression of Costimulatory Molecule Tim3 on NK Cells and Its Subsets in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of costimulatory molecule Tim3 and its subsets on NK cells in patients with acute myeloid leukemia.@*METHODS@#30 patients with acute myeloid leukemia treated in our hospital from August 2016 to August 2018 were randomly selected as the AML group, and 30 healthy persons in our hospital during the same period were randomly selected as the control group. The expression levels of CD56@*RESULTS@#The expression levels of CD56@*CONCLUSION@#The expression of costimulatory molecule Tim3 in NK cells and its subsets of patients with acute myeloid leukemia is down-regulated.

Melanotic neuroectodermal tumor of infancy: a clinicopathological case report

Abstract Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that affects mainly children under 1 year of age. A 4-month-old boy was referred for evaluation of a lesion with 1 month of evolution. Intra-oral examination detected a firm upon palpation submucosal nodular mass, measuring 1.5 cm in diameter, affecting the anterior maxillary alveolar ridge and covered by a slightly blue mucosa with evident telangiectasia. The patient underwent an incisional biopsy and histological and immunohistochemical analyses revealed nests of AE1/AE3 positive epithelioid cells with abundant melanin pigmentation. Other cell types, resembling neuroblasts, were also present and positive for CD56, synaptophysin and enolase. The diagnosis of MNTI was established and the patient was referred for treatment. Conservative surgical resection was performed along with 3 adjacent teeth under general anesthesia. The patient is in follow-up for 1,5 year without recurrence. Conservative surgical management of MNTI may be an alternative to maxillectomy, contributing to the patient´s quality of life.

Resumo Tumor neuroectodérmico melanótico da infância (TNMI) é um neoplasma raro que afeta principalmente crianças com idade abaixo de 1 ano. Um menino de 4 meses foi referenciado para avaliação de uma lesão com 1 mês de evolução. O exame intra-oral detectou uma massa nodular submucosa firme à palpação, medindo 1,5 cm de diâmetro, afetando rebordo alveolar anterior da maxila e recoberta por mucosa de coloração levemente azulada com telangiectasia evidente. O paciente foi submetido à biopsia incisional e as análises histológica e imunohistoquímica revelaram ninhos compostos por células com abundante pigmento de melanina, positivas para AE1/AE3. Outro tipo celular, semelhante à neuroblastos, também estava presente e foram positivas para CD56, sinaptofisina e enolase. O diagnóstico de TNMI foi estabelecido e o paciente encaminhado para tratamento. Ressecção cirúrgica conservadora sob anestesia geral ao longo de 3 dentes adjacentes foi realizada. O paciente está em acompanhamento há 1 ano e meio sem sinais de recorrência. O tratamento cirúrgico conservador do TNMI pode ser uma alternativa à maxilectomia, contribuindo para a qualidade de vida do paciente.

Expression of CD19 and CD56 in AML Patients with RUNX1-RUNX1T1 Mutation and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of RUNX1-RUNX1T1 expression level in bone marrow of patients with acute non-M3 myeloid leukemia (AML non-M3), and to understand the biological characteristics of RUNX1-RUNX1T1 positive AML expressing lymphoid antigens CD19, CD56 and its effect on the initially induced remission rate and prognosis.</p><p><b>METHODS</b>The expression level of RUNX1-RUNX1T1 in bone marrow of 200 patients with newly diagnosed AML (non-M3) was detected by real-time fluorescent Q-PCR, the expression level of lymphoid antigens was detected by flow cytometry, and the relationship of the initially induced remission rate (CR1) with the overall survival (OS) rate was analyzed, the CR1 and OS differences also were analyzed between CD56 and CD56 patients as well as CD19 and CD17 patients in RUNX1-RUNX1T1 positive patients with AML.</p><p><b>RESULTS</b>The CD56 patients at the initial diagnosis had lower CR1(P<0.05) in RUNX1-RUNX1T1 positive AML patients, the CR1 of CD19 patients was higher than that in CD19 patients at the initial diagnosis (P<0.05). The OS of CD56 patients was significantly high in comparison with CD56 patients (P<0.05), while the OS between CD19 patients and CD19 patients was not significantly different.</p><p><b>CONCLUSION</b>The bone marrow CD56 in RUNX1-RUNX1T1 positive AML patients suggests poor prognosis. The CD19 only correlates with CR1, but does not with OS.</p>

System Amplifying NK Cells Using Mononuclear Cell Culture / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To develop an easy method to amplify natural killer (NK) cells by using mononuclear cells in vitro, so as to lay the basis for NK cell therapy.</p><p><b>METHODS</b>Umbilical cord blood from 3 healthy full-term pregnant women was collected, and the peripheral blood mononuclear cells (PBMNC) were harvested by density gradient centrifugation. Each sample of PBMNC was divided into 3 groups: CD16mAb, CD3 mAb and CD16mAb+CD3mAb- groups. The culture flasks were pre-coated with CD16, CD3 or CD3 plus CD16 mAb. The PBMNCs were cultured in serum-free media containing autologous plasma, recombinant human IL-2, IL-15 and IL-21 for 14 days under the same conditions. The total viable cell count was calculated. Flow cytometry was used to determine the ratio of CD56CD3 cells, MTT assay was used to measure the killing rate of NK cells under different effector/target ratio, by using the K562 cells as the target cells.</p><p><b>RESULTS</b>After 14 days of culture, the total cell numbers of CD16mAb, CD3mAb and CD16mAb +CD3mAb groups increased by 45.71±5.54, 87.41±19.77 and 4.88±51.84 times, respectively, and those of CD3mAb group were significantly higher than the other 2 groups (P<0.05). The ratio of CD56CD3 cells before culture was 0.1663±0.0201, which was 0.8167±0.0500, 0.8077±0.0589 and 0.8077±0.0273 after incubation with CD16mAb, CD3mAb and CD16mAb +CD3mAb for 14 days, respectively (P>0.05). MTT test showed that the killing efficiencies were not significantly different among the 3 groups when the effector/target ratios were 1:1, 5:1 and 10:1 (P>0.05).</p><p><b>CONCLUSION</b>By incubation with anti-CD3 monoclonal antibody, IL-2, IL-15 and IL-21, the highly purified NK cells can be obtained from mononucleated cells, thus providing a simple method for NK cell therapy.</p>

Establishment of A Serum-Free Culture System Based on Heparin and Anti-CD16 Antibody for Expansion of Human Cord Blood NK Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish a novel method for ex vivo expansion of natural killer cells from human umbilical blood, so as to provide the basis for NK cell therapy.</p><p><b>METHODS</b>Mononucleated cells from human umbilical blood were harvested and suspended in a serum-free medium containing 5% autologous plasma, recombinant human IL-15 (50 ng/ml) and hydrocortisone sodium succinate (5×10 mol/L) at a concentration of 1.5×10/ml, then the cells were seeded into flasks pre-coated with heparin sodium (100 U/cm) or/and anti-human CD16 antibody (1 µg/cm). After culture for 2 weeks, the cells were harvested and counted. Ratios of CD3/CD56 of the cells were determined by flow cytometry. MTT test was performed to assess the cytotoxicity against K562 cells with graded ratios of effector/target cells.</p><p><b>RESULTS</b>In contrast to the cells in flasks without pre-coating, the attached colonies appeared predominantly within 1 week of culture from heparin- and antibody-coated groups. The cell numbers from the pre-coated groups were significantly higher than that of uncoated one after culture for 2 weeks. Furthermore, the ratios of CD3/CD56 cells were much higher in pre-coated groups, and that of the cells from flasks pre-coated with heparin and antibody were the highest (all the P values <0.01). MTT test showed that the cytotoxic activity of the cells stimulated by precoating were much more potent than that of the cells without the stimulation.</p><p><b>CONCLUSION</b>Advantageous expansion of NK cells can be achieved by precoating with heparin and anti-CD16 antibody, and also by supplement with IL-15 and hydrocortisone into the media, so the umbilical NK cells with high purity and potent cytotoxicity can be obtained.</p>

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed. Methods: We evaluated the gene expression profile of AT/RT samples to find new genetic factors contributing to the pathophysiology of the disease. We found target genes significantly differentially expressed between AT/RT and medulloblastoma (MB), the most common embryonal brain tumor. The mRNA expression was validated by quantitative real-time PCR and, at the protein level, expression was validated by immunohistochemistry in an independent set of tumors. Results: The Neural cell adhesion molecule 1 (NCAM1) gene was found to be consistently downregulated in AT/RT samples when compared to MB and normal brain tissue. Immunohistochemistry showed that the expression of NCAM1 in AT/RT was significantly lower than that of MB. Conclusion: NCAM1 is an important molecule involved in neuron-to-neuron and neuron-to-muscle adhesion during development. Downregulation of NCAM1 has been implicated in several human cancers suggesting that it might have a tumor repressor role. In this study we found a significantly reduced expression of NCAM1 in AT/RT when compared to MB and we suggest that this feature can be used as a diagnostic marker, along with demonstration of SMARCB1 (INI1) or SMARCA4 (BRG1) inactivation. The roles of NCAM1 in the pathophysiology of AT/RT are still to be determined (AU)

Diffuse large B-cell lymphoma with aberrant expression of CD56: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and significance of aberrant CD56 expression in diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>The clinical and pathologic profiles of 10 cases of DLBCL with aberrant expression of CD56 were investigated. Immunohistochemical staining, in-situ hybridization for Epstein-Barr virus encoded RNA and gene rearrangement for IgH and Igκ were carried out.</p><p><b>RESULTS</b>There were 6 male and 4 female patients. The medium age of patients was 46 years. All of them presented with extranodal lymphoma involvement, with gastrointestinal tract being the commonest site (5/10). Histologic examination showed that most of the atypical lymphoid cells were centroblast-like and demonstrated a diffuse growth pattern. Apoptosis and necrosis were identified in some cases. Immunohistochemical study showed that the tumor cells were positive for CD20 or CD79α and aberrantly expressed CD56. Five cases had the GCB phenotype while the remaining cases had the non-GCB phenotype, according to Hans classification. Bcl-6 was positive in most cases (9/10). All cases showed a high proliferation index by Ki-67. The tumor cells were negative for CD3ε, CD138 and granzyme B. In-situ hybridization for Epstein-Barr virus encoded RNA was performed in 7 cases and none of them showed positive signals. IgH gene rearranged bands were detected in 4 cases (4/6) and Igκ was detected in 3 cases (3/6). Follow-up data were available in 8 patients. Two patients died of disease progression within 5 to 13 months after diagnosis and the other 6 patients were alive 8 to 60 months after therapy.</p><p><b>CONCLUSIONS</b>DLBCL with aberrant expression of CD56 is rare. Most of them present with extranodal involvement, show high frequency of bcl-6 expression and high proliferation index. The patients often have good response to chemotherapy.</p>

Acute Myeloid Leukemia With MLL Rearrangement and CD4+/CD56+ Expression can be Misdiagnosed as Blastic Plasmacytoid Dendritic Cell Neoplasm: Two Case Reports

No abstract available.

Evaluation of CD56[dim] and CD56[bright] natural killer cells in peripheral blood of women with IVF failures

Infertility is an increasing medical and social problem. In vitro fertilization [IVF] has become a common and accessible treatment for a wide variety of indications that have variable outcomes. Natural killer [NK] cells have been identified as relevant immunological factors involved in reproductive success or failure. The aim of this study was to compare the percentage of peripheral blood CD56[+] [CD56[dim] and CD56[bright]] cells and the level of NK cell in patients with IVF failure with those of successful IVF control women. We assessed the level of CD56[dim] CD16[+] and CD56[bright] CD16[-] cells in 50 women under IVF treatment and compared between successful IVF and IVF failure with the flowcytometry technique. Of studied women, 68% did not response to IVF therapy and 32% had successful IVF, the level of CD56[dim] CD16[+] cells in women with IVF failure was significantly higher than successful IVF [p<0.0001] but the level of CD56[bright] CD16[-] cells was not significantly different between women with IVF failure and successful IVF [p=0.28]. The results of present study demonstrated that the level of NK cells as a risk factor is associated with pregnancy loss in women with IVF failure. However, number of sample in this study is low and further studies with more sample size are needed to be done. We suggest considering treatment option for women undergoing repeated IVF failure with increased percentage of CD56[dim] cells and the level of peripheral blood NK cell

Clinical features and survival analysis of patients with CD56 expression in de- novo acute myeloid leukemia with t（8;21） / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical features and survival of patients with CD56 expression in de- novo acute myeloid leukemia（AML）with t（8;21). .</p><p><b>METHODS</b>Clinical data of 82 de novo AML with t（8;21）who were newly diagnosed from Jan 2008 to Apr 2014 were analyzed retrospectively, 50 expressed CD56 and 32 not. Clinical characteristics and prognoses were compared between patients expressing and nonexpressing CD56.</p><p><b>RESULTS</b>There were no statistically significant differences in terms of age, gender, white blood cell count（WBC）, percentage of bone marrow blasts, extramedullary infiltration rate, the early mortality or the presence of additional cytogenetic abnormalities between CD56 + and CD56- groups（P＞0.05). The expressions of lymphatic antigens CD19 between CD56 + and CD56- groups showed significant difference （30.0% vs 53.1% , P=0.036). The complete remission and 3-year overall survival（OS）showed no significant differences between CD56+ and CD56-groups, while 3- year disease- free survival（DFS）showed significant differences（25.8% vs 46.9%, P=0.014). Multivariable analysis for DFS identified CD56 positivity as an independent predictor. DFS of who received allogeneic hematopoietic stem cell transplantation（HSCT）was better than those treated with intermediate- dose cytarabine/high dose cytarabine（IDAC）as postremission therapy.</p><p><b>CONCLUSION</b>The expression of CD56 in de-novo AML with t（8;21) appeared to be associated with poorer prognosis.</p>

Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset

Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.

Expression of p63, p40 and CK5/6 in small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC).</p><p><b>METHODS</b>Immunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC. The diagnostic value of these markers was evaluated.</p><p><b>RESULTS</b>The expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied. Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity (P < 0.01). On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8% (170/275), 85.5% (242/283) and 89.2% (248/278), respectively. The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 (P < 0.01). TTF1 was expressed in 77.2% (217/281).</p><p><b>CONCLUSIONS</b>p63 and p40 are expressed in a subset of SCLC. In contrast, CK5/6 is rarely positive in SCLC. An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.</p>