Deregulation of Ikaros expression in B-1 cells: New insights in the malignant transformation to chronic lymphocytic leukemia
| Autor: | Caio Perez Gomes, Celso Arrais Rodrigues, João Bosco Pesquero, Ana Flavia Popi, Olivia Fonseca Souza, Bárbara Bomfim Muniz Moraes, Nilmar Silvio Moretti, Marcelo Pitombeira de Lacerda, Sergio Schenkman, Vivian Cristina de Oliveira, Juliana Terzi Maricato |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Cytoplasm Chronic lymphocytic leukemia Immunology Population Receptors Antigen B-Cell Biology Models Biological Radiation Tolerance CD19 Ikaros Transcription Factor Mice 03 medical and health sciences 0302 clinical medicine LYN hemic and lymphatic diseases medicine Animals Humans Immunology and Allergy education B cell Aged Aged 80 and over B-Lymphocytes education.field_of_study Gene Expression Regulation Leukemic breakpoint cluster region Cell Biology Middle Aged medicine.disease Leukemia Lymphocytic Chronic B-Cell Mice Inbred C57BL Leukemia Cell Transformation Neoplastic 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biology.protein Female CD5 Protein Binding Signal Transduction |
| Zdroj: | Journal of Leukocyte Biology. 106:581-594 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1002/jlb.ma1118-454r |
| Popis: | Chronic lymphocytic leukemia (CLL) is a chronic form of leukemia that originates from an abnormal expansion of CD5+B-1 cells. Deregulation in the BCR signaling is associated with B-cell transformation. Contrariwise to B-2 cells, BCR engagement in B-1 cells results in low proliferation rate and increased apoptosis population, whereas overactivation may be associated with lymphoproliferative disorders. It has been demonstrated that several transcription factors that are involved in the B cell development play a role in the regulation of BCR function. Among them, Ikaros is considered an essential regulator of lymphoid differentiation and activation. Several reports suggest that Ikaros expression is deregulated in different forms of leukemia. Herein, we demonstrated that CLL cells show decreased Ikaros expression and abnormal cytoplasmic cell localization. These alterations were also observed in radioresistant B-1 cells, which present high proliferative activity, suggesting that abnormal localization of Ikaros could determine its loss of function. Furthermore, Ikaros knockdown increased the expression of BCR pathway components in murine B-1 cells, such as Lyn, Blnk, and CD19. Additionally, in the absence of Ikaros, B-1 cells become responsive to BCR stimulus, increasing cell proliferation even in the absence of antigen stimulation. These results suggested that Ikaros is an important controller of B-1 cell proliferation by interfering with the BCR activity. Therefore, altered Ikaros expression in CLL or radioresistant B-1 cells could determine a responsive status of BCR to self-antigens, which would culminate in the clonal expansion of B-1 cells. |
| Databáze: | OpenAIRE |
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