Increased CCL2 and IL-8 in the Bone Marrow Microenvironment in Acute Lymphoblastic Leukemia

dc.creatorde Vasconcellos, JF
dc.creatorLaranjeira, ABA
dc.creatorZanchin, NIT
dc.creatorOtubo, R
dc.creatorVaz, TH
dc.creatorCardoso, AA
dc.creatorBrandalise, SR
dc.creatorYunes, JA
dc.date2011
dc.dateAPR
dc.date2014-07-30T14:33:09Z
dc.date2015-11-26T16:32:06Z
dc.date2014-07-30T14:33:09Z
dc.date2015-11-26T16:32:06Z
dc.date.accessioned2018-03-28T23:13:24Z
dc.date.available2018-03-28T23:13:24Z
dc.identifierPediatric Blood & Cancer. Wiley Periodicals, Inc, v. 56, n. 4, n. 568, n. 577, 2011.
dc.identifier1545-5009
dc.identifierWOS:000287986700011
dc.identifier10.1002/pbc.22941
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60009
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60009
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1270397
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBackground. The interactions of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells have a positive impact on leukemia cell survival. In the present study, we proposed to identify and investigate the role of molecules critically involved in leukemia-microenvironment crosstalk. Procedure. Gene expression profiling analyses of BM mesenchymal stem cells (BMMSC) were performed following stimulation by ALL cells. CCL2 and IL-8 plasma levels were evaluated from, ALL patients and controls. Expression of the CCL2 and IL-8 receptors in ALL was determined by RT-PCR. The biological effects of CCL2, IL-8 or its neutralizing antibodies in primary precursor-B ALL and BMMSC cells were evaluated using in vitro assays. Results. Leukemia stimulation of BMMSC upregulated the expression of several inflammatory chemokines, including CCL2 and IL-8. The BM plasma levels of CCL2 and IL-8 in children at diagnosis were significantly higher than in healthy controls (P < 0.00)). Functional studies revealed that CCL2 and IL-8 enhanced the capacity of BMMSC to support adhesion of ALL cells. CCL2 and IL-8 were also found to enhance BMMSC survival and to increase their proliferation. ALL cells were not directly affected by CCL2 or IL-8. Conclusions. The leukemic BM microenvironment had increased levels of CCL2 and IL-8. These chemokines are known to have suppressive effects in normal hematopoiesis. Our data indicate that CCL2 and IL-8 have a positive impact on BMMSC survival, proliferation, and adhesiveness to ALL cells. Leukemia-associated CCL2 and IL-8 upregulation may represent one possible mechanism of microenvironment perversion in favor of ALL cells. Pediatr Blood Cancer 2011;56:568-577. (C) 2010 Wiley-Liss, Inc.
dc.description56
dc.description4
dc.description568
dc.description577
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.descriptionFAPESP [05/02390-4, 06/02083-7, 06/01158-3, 08/02106-2]
dc.descriptionCNPq [401122/05, 382.687/2008-6]
dc.languageen
dc.publisherWiley Periodicals, Inc
dc.publisherMalden
dc.publisherEUA
dc.relationPediatric Blood & Cancer
dc.relationPediatr. Blood Cancer
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectacute lymphoblastic leukemia
dc.subjectbone marrow microenvironment
dc.subjectCCL2
dc.subjectIL-8
dc.subjectChemokine Receptor Expression
dc.subjectMyeloid Progenitor Cells
dc.subjectStromal Cells
dc.subjectB-lineage
dc.subjectIn-vitro
dc.subjectDifferential Expression
dc.subjectLymphocytic-leukemia
dc.subjectSurvival
dc.subjectAdhesion
dc.subjectInterleukin-8
dc.titleIncreased CCL2 and IL-8 in the Bone Marrow Microenvironment in Acute Lymphoblastic Leukemia
dc.typeArtículos de revistas


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