Abstract:Aim of the studyFlow cytometry has an important role in diagnosis and classification of B-cell lymphoproliferative disorders (BCLPDs). However, in distinguishing chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma (SLL) only clinical criteria are available so far. Aim of the study was to determine differences in the expression of common B cell markers (CD22, CD79b and CD20) on the malignant lymphocytes in the peripheral blood samples of CLL and SLL patients.Material and methodsPeripheral blood s… Show more
“…Interestingly, at GSEA, they turned out to be significantly involved in interferon response and allograft rejection (as expected based on IFI16 known functions), as well as in other biological processes (Table 4). Of interest, these findings were, at least in part, validated by the evidence that several of the identified molecules are indeed expressed in MCL, showing sometimes a reduced expression mirroring that of IFI16, including CD22, BCL11A, FGD2, GPR18, PTPRC, HHEX, PPP1CB , and CTSS [42, 43, 44, 45, 46, 47]. Fig.…”
IFI16, member of the IFN-inducible PYHIN-200 gene family, modulates proliferation, survival and differentiation of different cell lineages. In particular, IFI16 expression, which is regulated during the differentiation of B cells, was recently studied in B-CLL as well. Here, we compared IFI16 expression in several lymphomas including Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma with respect to normal cell counterparts. We observed that IFI16 expression was significantly deregulated only in mantle cell lymphoma (p < 0.05). Notably, IFI16 was associated with the expression of genes involved in interferon response, cell cycle, cell death and proliferation and, interestingly, lipid and glucose metabolism, suggesting that IFI16 deregulation might be associated with relevant changes in cell biology. In our group of mantle cell lymphoma samples a correlation between patient survival and IFI16 expression was not detected even though mantle cell lymphoma prognosis is known to be associated with cell proliferation. Altogether, these results suggest a complex relationship between IFI16 expression and MCL which needs to be analyzed in further studies.
“…Interestingly, at GSEA, they turned out to be significantly involved in interferon response and allograft rejection (as expected based on IFI16 known functions), as well as in other biological processes (Table 4). Of interest, these findings were, at least in part, validated by the evidence that several of the identified molecules are indeed expressed in MCL, showing sometimes a reduced expression mirroring that of IFI16, including CD22, BCL11A, FGD2, GPR18, PTPRC, HHEX, PPP1CB , and CTSS [42, 43, 44, 45, 46, 47]. Fig.…”
IFI16, member of the IFN-inducible PYHIN-200 gene family, modulates proliferation, survival and differentiation of different cell lineages. In particular, IFI16 expression, which is regulated during the differentiation of B cells, was recently studied in B-CLL as well. Here, we compared IFI16 expression in several lymphomas including Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma with respect to normal cell counterparts. We observed that IFI16 expression was significantly deregulated only in mantle cell lymphoma (p < 0.05). Notably, IFI16 was associated with the expression of genes involved in interferon response, cell cycle, cell death and proliferation and, interestingly, lipid and glucose metabolism, suggesting that IFI16 deregulation might be associated with relevant changes in cell biology. In our group of mantle cell lymphoma samples a correlation between patient survival and IFI16 expression was not detected even though mantle cell lymphoma prognosis is known to be associated with cell proliferation. Altogether, these results suggest a complex relationship between IFI16 expression and MCL which needs to be analyzed in further studies.
“…This prediction was fulfilled as there is a significant positive correlation between CD22 expression on B cells and the reduction in HLA‐DP/DQ/DR after incubation with RBC (Figure 4d ). To further test the role of CD22, and to explore the relevance of the RBC suppressive mechanism to a human disease, we took advantage of findings that the lectin CD22 is expressed at only low levels by malignant B cells in patients with CLL [ 24 ]. We hypothesized that that these low lectin levels would result in refractoriness to RBC inhibition and so might contribute towards the activated phenotype [ 9 , 25 ] of CLL cells.…”
Non-immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B cells. Separation of RBC from peripheral blood mononuclear cells increased B-cell expression of HLA-DR/DP/DQ, whilst reconstitution reduced the levels of B-cell activation markers HLA-DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B cells required contact with RBC and was abrogated by either removal of sialic acids from RBC or blocking the corresponding lectin receptor CD22 on B cells. Chronic lymphocytic leukaemia B cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B cells whilst circulating in the bloodstream.
“…CD22 is a transmembrane glycoprotein that is widely expressed across malignant Bcell histologies [148]. In contrast to Zevalin ® and Bexxar ® , the anti-CD22 90 Y-epratuzumab tetraxetan can be administered without a loading dose of cold antibody.…”
Radioimmunoconjugates consist of a monoclonal antibody (mAb) linked to a radionuclide. Radioimmunoconjugates as theranostics tools have been in development with success, particularly in hematological malignancies, leading to approval by the US Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s lymphoma. Radioimmunotherapy (RIT) allows for reduced toxicity compared to conventional radiation therapy and enhances the efficacy of mAbs. In addition, using radiolabeled mAbs with imaging methods provides critical information on the pharmacokinetics and pharmacodynamics of therapeutic agents with direct relevance to the optimization of the dose and dosing schedule, real-time antigen quantitation, antigen heterogeneity, and dynamic antigen changes. All of these parameters are critical in predicting treatment responses and identifying patients who are most likely to benefit from treatment. Historically, RITs have been less effective in solid tumors; however, several strategies are being investigated to improve their therapeutic index, including targeting patients with minimal disease burden; using pre-targeting strategies, newer radionuclides, and improved labeling techniques; and using combined modalities and locoregional application. This review provides an overview of the radiolabeled intact antibodies currently in clinical use and those in development.
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