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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.)

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

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Author(s):
de Vasconcellos, Jaira Ferreira [1, 2] ; Albertoni Laranjeira, Angelo Brunelli [2] ; Tonin Zanchin, Nilson Ivo [3] ; Otubo, Rosemary [2] ; Vaz, Thais Haline [3] ; Cardoso, Angelo Almeida [4] ; Brandalise, Silvia Regina [2, 5] ; Yunes, Jose Andres [2]
Total Authors: 8
Affiliation:
[1] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, Campinas, SP - Brazil
[2] Ctr Infantil Boldrini, Lab Biol Mol, BR-13083210 Campinas, SP - Brazil
[3] Ctr Struct Mol Biol, Brazilian Synchrotron Light Lab, Campinas, SP - Brazil
[4] Indiana Univ Sch Med, IU Simon Canc Ctr, Indianapolis, IN - USA
[5] Univ Estadual Campinas, Fac Med Sci, Dept Pediat, Campinas, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: PEDIATRIC BLOOD & CANCER; v. 56, n. 4, p. 568-577, APR 2011.
Web of Science Citations: 24
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. (AU)

FAPESP's process: 05/02390-4 - Role of CCL2 and IL-8 on the survival and proliferation of childhood B-lineage acute lymphoblastic leukemia cells co-cultured with bone marrow stromal cells
Grantee:José Andrés Yunes
Support type: Regular Research Grants
FAPESP's process: 08/02106-2 - IGFBP7 role in chemotherapy resistance of Pediatric Acute Lymphoblastic Leukemia
Grantee:Angelo Brunelli Albertoni Laranjeira
Support type: Scholarships in Brazil - Doctorate