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Increased CCL2 and IL-8 in the bone marrow microenvironment in acute lymphoblastic leukemia
Pediatric blood & cancer, 2011-04, Vol.56 (4), p.568-577
de Vasconcellos, Jaíra Ferreira
Laranjeira, Angelo Brunelli Albertoni
Zanchin, Nilson Ivo Tonin
Otubo, Rosemary
Vaz, Thais Haline
Cardoso, Angelo Almeida
Brandalise, Silvia Regina
Yunes, José Andrés
2011
Details
Autor(en) / Beteiligte
de Vasconcellos, Jaíra Ferreira
Laranjeira, Angelo Brunelli Albertoni
Zanchin, Nilson Ivo Tonin
Otubo, Rosemary
Vaz, Thais Haline
Cardoso, Angelo Almeida
Brandalise, Silvia Regina
Yunes, José Andrés
Titel
Increased CCL2 and IL-8 in the bone marrow microenvironment in acute lymphoblastic leukemia
Ist Teil von
Pediatric blood & cancer, 2011-04, Vol.56 (4), p.568-577
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2011
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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 < 0.001). 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. © 2010 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 1545-5009, 1545-5017
eISSN: 1545-5017
DOI: 10.1002/pbc.22941
Titel-ID: cdi_proquest_miscellaneous_850561797
Format
–
Schlagworte
Acute lymphatic leukemia
,
acute lymphoblastic leukemia
,
Antibodies
,
Blast
,
Blood
,
Bone marrow
,
Bone Marrow Cells - metabolism
,
bone marrow microenvironment
,
Cancer
,
CCL2
,
Cell Adhesion
,
Cell proliferation
,
Cell Survival
,
Chemokine CCL2 - genetics
,
Chemokine CCL2 - metabolism
,
Chemokine CCL2 - physiology
,
Chemokines
,
Child
,
Child, Preschool
,
Children
,
Data processing
,
Female
,
Gene expression
,
Hemopoiesis
,
Humans
,
IL-8
,
Infant
,
Inflammation
,
Interleukin 8
,
Interleukin-8 - genetics
,
Interleukin-8 - metabolism
,
Interleukin-8 - physiology
,
Male
,
Mesenchyme
,
Microenvironments
,
Monocyte chemoattractant protein 1
,
Plasma levels
,
Polymerase chain reaction
,
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
,
Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
,
Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology
,
Prognosis
,
Signal Transduction
,
Stem cells
,
stromal cells
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