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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.<\/jats:p>","DOI":"10.1002\/jlb.ma1118-454r","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T13:24:45Z","timestamp":1562937885000},"page":"581-594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deregulation of Ikaros expression in B-1 cells: New insights in the malignant transformation to chronic lymphocytic leukemia"],"prefix":"10.1093","volume":"106","author":[{"given":"Vivian Cristina","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo Pitombeira","family":"de Lacerda","sequence":"additional","affiliation":[{"name":"Disciplina de Hematologia e Hemoterapia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara Bomfim Muniz","family":"Moraes","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caio Perez","family":"Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Molecular, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Terzi","family":"Maricato","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia Fonseca","family":"Souza","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Schenkman","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Bosco","family":"Pesquero","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Molecular, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilmar Silvio","family":"Moretti","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celso Arrais","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Disciplina de Hematologia e Hemoterapia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-4181","authenticated-orcid":false,"given":"Ana Flavia","family":"Popi","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de S\u00e3o Paulo , Sao Paulo,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"2026041420270139500_jlb10451-cit-0001","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/ajh.24282","article-title":"Chronic lymphocytic leukemia (CLL)-Then and now","volume":"91","author":"Rai","year":"2016","journal-title":"Am J 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