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

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

Author Vasconcellos, Jaira Ferreira de Google Scholar
Albertoni Laranjeira, Angelo Brunelli Google Scholar
Tonin Zanchin, Nilson Ivo Google Scholar
Otubo, Rosemary Google Scholar
Vaz, Thais Haline Google Scholar
Cardoso, Angelo Almeida Google Scholar
Brandalise, Silvia Regina Google Scholar
Yunes, Jose Andres Google Scholar
Institution Ctr Infantil Boldrini
Universidade Estadual de Campinas (UNICAMP)
Ctr Struct Mol Biol
Indiana Univ Sch Med
Universidade Federal de São Paulo (UNIFESP)
Abstract Background. 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.
Keywords acute lymphoblastic leukemia
bone marrow microenvironment
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 05/02390-4
FAPESP: 06/02083-7
FAPESP: 06/01158-3
FAPESP: 08/02106-2
CNPq: 401122/05
CNPq: 382.687/2008-6
Date 2011-04-01
Published in Pediatric Blood & Cancer. Malden: Wiley Periodicals, Inc, v. 56, n. 4, p. 568-577, 2011.
ISSN 1545-5009 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 568-577
Access rights Closed access
Type Article
Web of Science ID WOS:000287986700011

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