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Takeshi Tsubata
B cells express various inhibitory co-receptors including CD22, CD72, and Siglec-G. These receptors contain immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region. Although many of the inhibitory co-receptors negatively regulate BCR signaling by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1), different inhibitory co-receptors have distinct functional properties. CD22, Siglec-G, and CD72 preferentially regulate tonic signaling in conventional B cells, B-1 cell homeostasis, and development of lupus-like disease, respectively...
2018: Frontiers in Immunology
Edward A Clark, Natalia V Giltiay
CD22 (Siglec 2) is a receptor predominantly restricted to B cells. It was initially characterized over 30 years ago and named "CD22" in 1984 at the 2nd International workshop in Boston (1). Several excellent reviews have detailed CD22 functions, CD22-regulated signaling pathways and B cell subsets regulated by CD22 or Siglec G (2-4). This review is an attempt to highlight recent and possibly forgotten findings. We also describe the role of CD22 in autoimmunity and the great potential for CD22-based immunotherapeutics for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE)...
2018: Frontiers in Immunology
Yukio Kobayashi
The treatment outcomes of adult acute lymphoblastic leukemia (ALL) have improved. Furthermore, the introduction of pediatric specific therapies has enhanced ALL treatment results in adolescents and young adult (AYAs). Age-related molecular signatures have also been identified, such as Philadelphia chromosome (Ph)-like ALL and DUX4/ERG gene-associated ALL. The measurement of minimal residual disease (MRD) has enabled the early detection of patients susceptible to relapse, and they become candidates for hematopoietic stem cell transplantation (HSCT)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Yue-Fang Wang, Ge Zhang, Yong-Mei Jiang, Ju Gao
OBJECTIVE: To determine whether immune differentiation antigen is related with clinical features and minimal residual disease (MRD) in childhood B-cell precursor acute lymphoblastic leukemia (B-ALL), who were treated with CCCG-ALL-2015 protocol. METHODS: A retrospective analysis was conducted in 132 B-ALL children, Multiparametric flow cytometry was used to analyze the immunophenotypes. The children were divided into 2 groups by MRD>0.1% on d 19 and / or d 46 after chemotherapy...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Deepa Bhojwani, Richard Sposto, Nirali N Shah, Vilmarie Rodriguez, Constance Yuan, Maryalice Stetler-Stevenson, Maureen M O'Brien, Jennifer L McNeer, Elizabeth A Raetz, Mignon L Loh, Susan R Rheingold
Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens...
September 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Yi-Qun Li, Li Sun, Jun Li
B cells in fish are proven to be endocytic and have a great contribution to innate immunity like phagocytosis. In this study, the endocytic capacity and the corresponding internalization pathways of IgM+ B cells in Japanese flounder (Paralichthys olivaceus) were investigated. The results showed that IgM+ B cells in peripheral blood leukocytes (PBL) and splenic leukocytes (SL) exhibited different abilities to ingest 0.5 μm and 1 μm latex beads through macropinocytosis-dependent endocytic pathway. Japanese flounder CD22 (PoCD22) co-stimulatory signals were identified to be essential for the innate immune responses in B cells...
September 25, 2018: Fish & Shellfish Immunology
(no author information available yet)
The FDA approved moxetumomab pasudotox-tdfk, a CD22-directed recombinant immunotoxin, for patients with relapsed/refractory hairy cell leukemia who have not responded to at least two prior treatments, including a purine nucleoside analogue.
September 27, 2018: Cancer Discovery
Sindhu Cherian, Maryalice Stetler-Stevenson
The use of targeted therapy is growing in the setting of hematopoietic neoplasms. Flow cytometry is a cornerstone of residual disease monitoring post therapy in this group of malignancies. Often, there is overlap between antigens targeted by immunotherapies and gating reagents utilized for population identification by flow cytometry. Such overlap can render a previously excellent gating reagent inadequate for disease detection. Recently, several anti-CD19 T cell-engaging immunotherapeutic agents and an anti-CD22 immunotoxin have been FDA approved for use in B lymphoblastic leukemia (B-LL), with an anti-CD22 T cell-engaging agent in development...
October 2018: Current Protocols in Cytometry
Lamia Özgör, Sarah J Meyer, Marina Korn, Klara Terörde, Lars Nitschke
Siglec-G and CD22 are inhibitory receptors on B cells and play an important role in the maintenance of tolerance. Although both molecules are expressed on all B cell populations at a similar level, Siglec-G was found to regulate exclusively B1a cells, whereas CD22 functions as an inhibitory receptor specifically on B2 cells. It is known that the mechanistic function of both Siglecs is regulated by sialic acid binding in a reciprocal manner, although it was not known until now how B cells would act when both Siglec-G and CD22 lack their ability to bind sialic acids...
October 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
George B McDonald, James W Freston, James L Boyer, Laurie D DeLeve
BACKGROUND AND RATIONALE: Treatment of hematologic malignancy with antibody-drug conjugates (ADC) may cause liver injury. ADCs deliver a toxic moiety into antigen-expressing tumor cells but may also injure hepatic sinusoids (Sinusoidal Obstruction Syndrome, SOS). We studied patients who received an anti-CD22-calicheamicin conjugate (inotuzumab ozogamicin) to gain insight into mechanisms of sinusoidal injury, as there are no CD22+ cells in the normal liver but non-specific uptake of ADCs by liver sinusoidal endothelial cells...
August 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Katherine C Pehlivan, Brynn B Duncan, Daniel W Lee
PURPOSE OF REVIEW: Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy. RECENT FINDINGS: CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting...
October 2018: Current Hematologic Malignancy Reports
Anh Cao, Nouf Alluqmani, Fatima Hifza Mohammed Buhari, Laabiah Wasim, Logan K Smith, Andrew T Quaile, Michael Shannon, Zaki Hakim, Hossai Furmli, Dylan M Owen, Alexei Savchenko, Bebhinn Treanor
The galectin family of secreted lectins have emerged as important regulators of immune cell function; however, their role in B-cell responses is poorly understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we show enhanced BCR microcluster formation and signaling in galectin-9-deficient B cells. Notably, treatment with exogenous recombinant galectin-9 nearly completely abolishes BCR signaling. We investigated the molecular mechanism for galectin-9-mediated inhibition of BCR signaling using super-resolution imaging and single-particle tracking...
August 17, 2018: Nature Communications
N Giovannone, J Liang, A Antonopoulos, J Geddes Sweeney, S L King, S M Pochebit, N Bhattacharyya, G S Lee, A Dell, H R Widlund, S M Haslam, C J Dimitroff
Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9)...
August 17, 2018: Nature Communications
Carole Nagant, Daniele Casula, Anne Janssens, Vo Thanh Phuong Nguyen, Brigitte Cantinieaux
INTRODUCTION: The discrimination of leukemia lymphoblasts (LB) in diagnosis and follow-up of B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) by multiparameter flow cytometry (MFC) may be difficult due to the presence of hematogones (HG). The aim of this study was to compare lymphoblasts of BCP-ALL and HG for the expression of the most discriminating antigens. METHODS: A total of 82 bone marrow samples (39 BCP-ALL and 43 patients with HG) were analyzed using MFC...
August 16, 2018: International Journal of Laboratory Hematology
Katerina Cerna, Jan Oppelt, Vaclav Chochola, Katerina Musilova, Vaclav Seda, Gabriela Pavlasova, Lenka Radova, Maddalena Arigoni, Raffaele A Calogero, Vladimir Benes, Martin Trbusek, Yvona Brychtova, Michael Doubek, Jiri Mayer, Sarka Pospisilova, Marek Mraz
The variable clinical course in chronic lymphocytic leukaemia (CLL) largely depends on p53 functionality and B-cell receptor (BCR) signalling propensity; however, it is unclear if there is any crosstalk between these pathways. We show that DNA damage response (DDR) activation leads to down-modulating the transcriptional factor FOXP1, which functions as a positive BCR signalling regulator and its high levels are associated with worse CLL prognosis. We identified microRNA (miRNA) miR-34a as the most prominently upregulated miRNA during DDR in CLL cells in vitro and in vivo during FCR therapy (fludarabine, cyclophosphamide, rituximab)...
August 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xue-Fei Zhao, Hong-Yan Wang, Xu Zhao, Huan-Chen Cheng, Wei Li, Sheng-Wei Liu, Lin Qiu, Jun Ma
OBJECTIVE: To retrospectively analyze the immunophenotyping, fusion gene and gene mutation of 30 acute lymphoblastic leukemia (ALL) cases and to investigate the relationship between the analysis results and the clinical therapeutic effect and prognosis. METHODS: Thirty All phtients were collected from the First Hospital of Harbin, Institute of Hematology and Oncology Department of Pediatrics from August 2015 to June 2016. According to the classification of FAB standard, 27 cases were B system ALL, 3 cases were T system ALL...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Takayuki Yamamoto, Qi Li, Hidetaka Hara, Liaoran Wang, Hongmin Zhou, Juan Li, Devin E Eckhoff, A Joseph Tector, Edwin C Klein, Ray Lovingood, Mohamed Ezzelarab, David Ayares, Yi Wang, David K C Cooper, Hayato Iwase
BACKGROUND: In the pig-to-baboon artery patch model with no immunosuppressive therapy, a graft from an α1,3-galactosyltransferase gene-knockout (GTKO) pig elicits a significant anti-nonGal IgG response, indicating sensitization to the graft. A costimulation blockade-based regimen, e.g., anti-CD154mAb or anti-CD40mAb, prevents sensitization. However, neither of these agents is currently FDA-approved. The aim of the present study was to determine the efficacy of FDA-approved agents on the T and B cell responses...
August 6, 2018: Transplant Immunology
Zaina T Al-Salama
The intravenous CD22-directed antibody drug conjugate inotuzumab ozogamicin (Besponsa® ) is approved in several countries including in the USA, EU and Japan, as monotherapy for the treatment of adults with relapsed/refractory B-cell acute lymphoblastic leukaemia (ALL). In adults with relapsed/refractory B-cell ALL who had received one or two prior treatment regimens, inotuzumab ozogamicin was associated with significantly higher rates of complete remission (including complete remission with incomplete haematological recovery) [CR/CRi] than standard therapy in the pivotal INO-VATE ALL trial...
August 2018: Targeted Oncology
Dilip K Das
Some of the limitations of fine needle aspiration (FNA) in the cytodiagnosis of lymphoma include problems encountered in differentiating reactive hyperplasia from low-grade non-Hodgkin lymphoma (NHL), lower cytodiagnostic accuracy for NHL with a follicular (nodular) pattern and nodular sclerosis type of classical Hodgkin lymphoma (HL), and overlapping morphological features between T-cell-rich B-cell lymphoma (TCRBCL), anaplastic large cell lymphoma (ALCL), and HL. Immunocytochemistry may be of help in such situations...
July 2018: Journal of Cytology
Ilana R Yurkiewicz, Lori Muffly, Michaela Liedtke
Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin...
2018: Drug Design, Development and Therapy
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