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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PEDIATRIC BLOOD & CANCER; v. 56, n. 4, p. 568-577, APR 2011.
• Citações Web of Science: 24

Resumo

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)

• Processo FAPESP: 08/02106-2 - IGFBP7 e a quimioresistência da Leucemia Linfóide Aguda Pediátrica
• Beneficiário: Angelo Brunelli Albertoni Laranjeira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 05/02390-4 - Ação da CCL2 e IL-8 na sobrevivência e proliferação da leucemia linfóide aguda pediátrica, em sistema de co-cultura com células do estroma da medula óssea
• Beneficiário: José Andrés Yunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/02083-7 - Caracterizacao funcional de proteinas envolvidas no controle da expressao genica.
• Beneficiário: Nilson Ivo Tonin Zanchin
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/01158-3 - Acao da ccl2 na sobrevivencia e proliferacao da leucemia linfoide aguda pediatrica, em sistema de co cultura com celulas do estroma da medula ossea.
• Beneficiário: Jaíra Ferreira de Vasconcellos
• Modalidade de apoio: Bolsas no Brasil - Doutorado