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Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
B-cell type lymphomas characteristically express CD20, CD19, CD10, and CD79a and may express surface immunoglobulin (sIg) and bcl-6. Translocations t(8;14), t(2;8), and t(8;22) and MYC rearrangements are typical. B-lymphoblastic lymphoma often shows IGH rearrangements, whilst T-lymphoblastic lymphoma show T-cell receptor rearrangements, and abnormalities of NOTCH/FBXW7 and PTEN pathways. ALCL typically express CD30 and carry a translocation causing fusion of the anaplastic lymphoma kinase (ALK) gene to neucleophosmin (NPM/ALK).
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
The B cell receptor (BCR) complex is constituted by sIg associated with CD79a/Igα) and CD79b/Igβ (Figure 10.3). Antigen recognition occurs though the sIg, whereas Igα and Igβ mediate signal transduction. After antigen binding, the recruitment of tyrosine kinase to the cytoplasmic domains of Igα and Igβ initiates the activation cascade. The major kinase that is recruited to the BCR complex is Bruton's tyrosine kinase (Btk). Congenital Btk deficiency is associated with a block in B-cell differentiation, demonstrating that signals delivered through the fully assembled BCR and associated kinases are necessary for B cell development during ontogeny.
The Non-Hodgkin’s Lymphomas and Plasma Cell Dyscrasias
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Lynne V. Abruzzo, L. Jeffrey Medeiros
The immunophenotype of plasma cell myeloma and plasmacytoma is similar to benign plasma cells. Like benign plasma cells, the neoplastic cells express cytoplasmic, but not surface, immunoglobulin. However, unlike reactive process, which contains a mixture of kappa-and lambda-positive plasma cells, neoplastic plasma cells express monoclonal immunoglobulin and show a light chain restriction. A population is said to demonstrate a light chain restriction when the ratio of one light chain type to the other exceeds 16:1. Both benign and malignant plasma cells fail to express most B-cell-associated antigens, such as CD19, CD20, and CD22. However, they express the B-cell-associated antigen CD79a, which is also expressed on plasma cells. Like benign plasma cells, the neoplastic cells are usually negative for CD45 (leukocyte common antigen), positive for CD38 and the mature plasma cell antigens, PC-1, and PCA-1. They also may express epithelial membrane antigen (EMA). Neoplastic plasma cells, but not benign plasma cells, stain with the antibody MB2, and also often epxress CD56, an adhesion molecule that is associated with natural killer cell differentiation. A minority of cases express CD10 (CALLA), and markers of myelomonocytic differentiation, such as CD11b, CD11c, CD13, CD15, and CD33.
Analysis of Vitreous Samples by the Cellient® Automated Cell Block System: A Six-year Review of Specimens in a Uveitis Population
Published in Ocular Immunology and Inflammation, 2022
Tine Jacobs, Dietmar Rudolf Thal, Birgit Weynand, Joachim Van Calster, Rita Van Ginderdeuren
In all diagnostic cases, CD68-positive macrophages were found; in all cases of active inflammation and malignancies, CD3-positive T lymphocytes were also present. In all cellular specimens, a routine B lymphocyte marker (CD79a/Pax5) was tested, and this marker was negative except for lymphoma cases; the only other exception was chronic inflammation of infectious origin, in which less than 5% CD138 positive plasma cells were detected. In 86 of 226 cases with active chronic inflammation, granulomatous inflammation was diagnosed. All these cases presented with clusters of epithelioid cells and/or giant cells and were confirmed with a positive CD68 staining. Of the 86 cases with granulomatous inflammation, an elevated CD4/CD8 ratio above 3 was found in 39 cases (45%) as indication of (ocular) sarcoidosis. All confirmed pulmonary sarcoidosis cases had an elevated CD4/CD8 ratio in the vitreous.
Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy
Published in Expert Review of Hematology, 2022
Salvatore Perrone, Paolo Lopedote, Mario Levis, Alice Di Rocco, Stephen Douglas Smith
Antibody-drug conjugates represent a major class of novel therapies in lymphoma, and offer the potential for targeted delivery of chemotherapy agents to malignant cells expressing B-cell specific surface antigens. The CD79 molecule, is a heterodimer composed of an Igα (CD79a) and Igβ (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It transmits a signal after antigen binding and it appears before the pre-B-cell stage, and the CD79a chain can still be present at the plasma cell stage [59]. Polatuzumab vedotin-piiq (pola) in combination with BR was approved in 2019 by the FDA and the EMA (Figure 2) for r/r DLBCL who failed ≥2 lines of therapy, for the results of the GO29365 trial and is now incorporated in the National Cancer Care Network (NCCN) guidelines for patients in this setting [60].
Polatuzumab vedotin for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma
Published in Expert Opinion on Biological Therapy, 2021
Mary-Kate Malecek, Marcus P. Watkins, Nancy L. Bartlett
Polatuzumab vedotin (Genentech, South San Francisco, CA, USA) is an ADC comprised of an anti-CD79b monoclonal antibody conjugated to monomethyl auristatin (MMAE), a microtubule-disrupting cytotoxin (Box 1). CD79b is a signaling component of the B cell receptor (BCR) complex and is expressed almost exclusively on normal and malignant B cells [53]. CD79a and CD79b expression precedes CD20 expression and disappears in later stages of B cell ontogeny. BCR cross-linking triggers signaling, targeting it to the lysosome-like major histocompatibility complex class II positive compartment. This allows ADC internalization, lysosomal degradation of the linker, and release of the drug only in the targeted cells. CD79b is expressed in DLBCL, mantle cell lymphoma, Burkitt lymphoma, and follicular lymphoma , and is, therefore, an appealing target for the development of novel therapeutics [54].