T acute lymphoblastic leukaemia (T-ALL) cells arise inside the thymus and in most cases, early during the clinical course, migrate to bone marrow (BM). In this study, we explored whether the chemokine CXCL12, produced by BM stromal cells, could affect cytokine production of T- ALL cells. Treatment of cells derived from adult T-ALL patients with CXCL12 induced a significant increased pro- duction of IL-8 but was ineffective on IL-1, TNF, or IL-10 production. Real Time PCR and colorimetric quantification assay confirmed the IL-8 increased expression also at mRNA level. We then investigated the role of CXCL12 produced by BM stromal cells in inducing IL-8 in primary T-ALL cells. To address this issue, we performed lympho- stromal co-cultures between normal human BM stroma and primary T-ALL cells. After co-culture, T-ALL cells were isolated from BM cells by Fluorescence Activated Cell Sorting and analyzed for the presence of IL-8 mRNA. The inter- action with BM stroma induced increased expression of IL-8 mRNA in T-ALL patients. The presence in the co-culture of antibody blocking the CXCL12 receptor, CXCR4, completely inhibited the IL-8 induction mediated by BM stroma. Our results implicate a novel function for CXCL12 in regulating IL-8 production in T-ALL within the BM microenvironment, and point out the role of bystander cells in influencing cytokine expression profile of T-ALL.

HUMAN T-LYMPHOBLASTIC LEUKAEMIA CELLS PRODUCE IL-8 IN RESPONSE TOCXCL12 SECRETED BY NORMAL BONE MARROW STROMA

SCUPOLI, Maria;MALPELI, Giorgio;VINANTE, Fabrizio;DONADELLI, Massimo;KRAMPERA, Mauro;SCARPA, Aldo;PALMIERI, Marta;PIZZOLO, Giovanni
2005

Abstract

T acute lymphoblastic leukaemia (T-ALL) cells arise inside the thymus and in most cases, early during the clinical course, migrate to bone marrow (BM). In this study, we explored whether the chemokine CXCL12, produced by BM stromal cells, could affect cytokine production of T- ALL cells. Treatment of cells derived from adult T-ALL patients with CXCL12 induced a significant increased pro- duction of IL-8 but was ineffective on IL-1, TNF, or IL-10 production. Real Time PCR and colorimetric quantification assay confirmed the IL-8 increased expression also at mRNA level. We then investigated the role of CXCL12 produced by BM stromal cells in inducing IL-8 in primary T-ALL cells. To address this issue, we performed lympho- stromal co-cultures between normal human BM stroma and primary T-ALL cells. After co-culture, T-ALL cells were isolated from BM cells by Fluorescence Activated Cell Sorting and analyzed for the presence of IL-8 mRNA. The inter- action with BM stroma induced increased expression of IL-8 mRNA in T-ALL patients. The presence in the co-culture of antibody blocking the CXCL12 receptor, CXCR4, completely inhibited the IL-8 induction mediated by BM stroma. Our results implicate a novel function for CXCL12 in regulating IL-8 production in T-ALL within the BM microenvironment, and point out the role of bystander cells in influencing cytokine expression profile of T-ALL.
Acute Lymphoblastic Leukemia; cytokines; Tumor Microenvironment
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/627256
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