IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

dc.creatorLaranjeira, A. B. A.
dc.creatorde Vasconcellos, J. F.
dc.creatorSodek, L.
dc.creatorSpago, M. C.
dc.creatorFornazim, M. C.
dc.creatorTone, L. G.
dc.creatorBrandalise, S. R.
dc.creatorNowill, A. E.
dc.creatorYunes, J. A.
dc.date2012
dc.date2013-09-19T18:06:15Z
dc.date2016-07-01T14:54:07Z
dc.date2013-09-19T18:06:15Z
dc.date2016-07-01T14:54:07Z
dc.date.accessioned2018-03-29T01:55:04Z
dc.date.available2018-03-29T01:55:04Z
dc.identifierLeukemia. Nature Publishing Group, v.26, n.5, p.1001-1011, 2012
dc.identifier0887-6924
dc.identifierWOS:000303883500019
dc.identifier10.1038/leu.2011.289
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/2010
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/2010
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1308702
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionThe interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P = 0.003) in precursor B-cell Ph(-) ALL patients (n = 147) treated with a contemporary polychemotherapy protocol.
dc.description26
dc.description5
dc.description1001
dc.description1011
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherNature Publishing Group
dc.publisherLondon
dc.relationLeukemia
dc.rightsfechado
dc.sourceWOS
dc.subjectIGFBP7
dc.subjectacute lymphoblastic leukemia
dc.subjectbone marrow stromal cells
dc.subjectasparaginase
dc.subjectdrug resistance
dc.subjectinsulin
dc.subjectDEXAMETHASONE-INDUCED APOPTOSIS
dc.subjectBONE-MARROW MICROENVIRONMENT
dc.subjectGROWTH-FACTOR
dc.subjectBINDING-PROTEINS
dc.subjectPREDNISOLONE RESISTANCE
dc.subjectDRUG-SENSITIVITY
dc.subjectINSULIN
dc.subjectEXPRESSION
dc.subjectCHILDREN
dc.subjectSURVIVAL
dc.titleIGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase
dc.typeArtículos de revistas


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