Mutations known from B-cell lymphoid malignancies are not found in CD34+ stem cells from patients with lymphoma

2021 ◽  
pp. 1-4
Author(s):  
Simon Husby ◽  
Francesco Favero ◽  
Francisco G. Rodriguez-Gonzalez ◽  
Lesley A. Sutton ◽  
Eva K. Haastrup ◽  
...  
Keyword(s):  
Stem Cells ◽  
B Cell ◽  
Lymphoid Malignancies

scholarly journals Pathogenic B‐cell receptor signaling in lymphoid malignancies: New insights to improve treatment

2019 ◽  
Vol 291 (1) ◽  
pp. 190-213 ◽  
Author(s):  
Ryan M. Young ◽  
James D. Phelan ◽  
Wyndham H. Wilson ◽  
Louis M. Staudt
Keyword(s):  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Lymphoid Malignancies ◽  
Improve Treatment ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

scholarly journals EBF1 is expressed in pericytes and contributes to pericyte cell commitment

2021 ◽  
Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Cell Lineage ◽  
Cell Maturation ◽  
Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

scholarly journals The biology behind B-cell lymphoma 2 as a target in chronic lymphocytic leukemia

2016 ◽  
Vol 7 (6) ◽  
pp. 321-329 ◽  
Author(s):  
Valentín Ortíz-Maldonado ◽  
Pablo Mozas ◽  
Julio Delgado
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mitochondrial Pathway ◽  
Therapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Hallmarks Of Cancer ◽  
Lymphoid Malignancies

B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main ‘hallmarks of cancer’, BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect.

scholarly journals Mesenchymal stem cells suppress B-cell terminal differentiation

2009 ◽  
Vol 37 (5) ◽  
pp. 604-615 ◽  
Author(s):  
Sadaki Asari ◽  
Shin Itakura ◽  
Kevin Ferreri ◽  
Chih-Pin Liu ◽  
Yoshikazu Kuroda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Terminal Differentiation

scholarly journals NF-κB2 mutation targets TRAF1 to induce lymphomagenesis

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 743-751 ◽  
Author(s):  
Baochun Zhang ◽  
Zhe Wang ◽  
Tai Li ◽  
Erdyni N. Tsitsikov ◽  
Han-Fei Ding
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
Apparent Effect ◽  
Antiapoptotic Protein ◽  
Lymphoid Malignancies ◽  
Targeted Expression ◽  
Antiapoptotic Activity ◽  
B Cell Homeostasis ◽  
Cytokine Deprivation

Abstract The NF-κB2 gene is recurrently mutated in human lymphoid malignancies. However, a causal relationship between NF-κB2 mutation and lymphomagenesis has not been established. It is also unclear how the mutation may lead to lymphoid malignancies. We report the generation of transgenic mice with targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, in lymphocytes. The transgenic mice display a marked expansion of peripheral B cell populations and develop predominantly small B cell lymphomas. p80HT expression has no apparent effect on the proliferation of B cells, but renders them specifically resistant to apoptosis induced by cytokine deprivation and mitogenic stimulation. Lymphocytes and lymphoma cells from p80HT mice express high levels of TRAF1, an antiapoptotic protein also implicated in lymphoid malignancies. p80HT binds the TRAF1 promoter in vivo and activates TRAF1 transcription. Moreover, TRAF1 knockdown abrogates the antiapoptotic activity of p80HT and TRAF1 deficiency reestablishes B cell homeostasis in p80HT mice. These findings demonstrate NF-κB2 mutation as an oncogenic event in vivo and suggest a molecular pathway for TRAF1 activation in the pathogenesis of lymphomas.

Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 660-669 ◽  
Author(s):  
Maria Teresa Sabrina Bertilaccio ◽  
Giorgia Simonetti ◽  
Antonis Dagklis ◽  
Martina Rocchi ◽  
Tania Veliz Rodriguez ◽  
...  
Keyword(s):  
Immune Response ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Adaptive Immune Response ◽  
Lymphocytic Leukemia ◽  
Fine Tuning ◽  
Terminal Phase ◽  
Lymphoid Malignancies ◽  
History Of ◽  
Molecular Patterns

Abstract Inflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R–like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eμ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.

Immunoregulatory effects of dental mesenchymal stem cells on T and B lymphocyte responses in primary Sjögren's syndrome

Immunotherapy ◽  
2022 ◽  
Author(s):  
Deniz Genç ◽  
Burcu Günaydın ◽  
Serhat Sezgin ◽  
Akın Aladağ ◽  
Emine Figen Tarhan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Lymphocyte Responses

Background: In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), which is an autoimmune disease resulting from keratoconjunctivitis sicca and xerostomia. Methods: Mononuclear cells isolated from pSS patients cultured with or without dental MSCs and analyzed for lymphocyte responses via flow cytometry. Results: Dental-follicle (DF)- and dental-pulp (DP)-MSCs downregulated CD4+ T lymphocyte proliferation by increasing Fas-ligand expression on T lymphocytes and FoxP3 expressing Tregs, and decreasing intracellular IFN-γ and IL-17 secretion in pSS patients. DF-MSCs decreased the plasma B cell ratio in the favor of naive B cell population in pSS patients' mononuclear cells. Conclusion: DF- and DP-MSCs can be the new cellular therapeutic candidates for the regulation of immune responses in pSS.

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