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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Deregulation of Ikaros expression in B-1 cells: New insights in the malignant transformation to chronic lymphocytic leukemia

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Author(s):
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de Oliveira, Vivian Cristina [1] ; de Lacerda, Marcelo Pitombeira [2] ; Muniz Moraes, Barbara Bomfim [1] ; Gomes, Caio Perez [3] ; Maricato, Juliana Terzi [1] ; Souza, Olivia Fonseca [1] ; Schenkman, Sergio [1] ; Pesquero, Joao Bosco [3] ; Moretti, Nilmar Silvio [1] ; Rodrigues, Celso Arrais [2] ; Pop, Ana Flavia [1]
Total Authors: 11
Affiliation:
[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Disciplina Hematol & Hemoterapia, Escola Paulista Med, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Biol Mol, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Journal of Leukocyte Biology; v. 106, n. 3, SI, p. 581-594, SEP 2019.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 11/51973-3 - Cell signaling mechanism of Trypanosoma in response to nutritional alterations and genotoxic agents
Grantee:Sergio Schenkman
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/01986-2 - Ikaros: role in the BCR- signaling in B-1 cells and association with chronic lymphocytic leukemia
Grantee:Ana Flavia Popi
Support type: Regular Research Grants
FAPESP's process: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges
Grantee:João Bosco Pesquero
Support type: Research Projects - Thematic Grants