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Transcriptional profiling of cytokines and its receptors in primary murine lymphoblastoid cells (pML cells)

ABSTRACT: Transcriptional profiling of cytokines and its receptors in primary murine lymphoblastoid cells (pML cells), which are lymphomatous cells from HTLV-1 TAX transgenic mice. ATL is a T-cell malignancy caused by HTLV-I, and presents as an aggressive leukemia with characteristic widespread leukemic cell infiltration into visceral organs and skin. The molecular mechanisms associated with leukemic cell infiltration are poorly understood. We have employed mouse models of ATL to investigate the role of chemokines in this process. Transfer of splenic lymphomatous cells from transgenic to SCID mice rapidly reproduces a leukemia and lymphoma which is histologically identical to human disease. It could be shown that lymphomatous cells exhibit specific chemotactic activity in response to SDF-1α. Lymphomatous cells exhibited surface expression of CXCR4, the specific receptor of SDF-1α and chemotaxis was associated with down regulation of CXCR4 expression and phosphorylation of intracellular ERK1/2. AMD3100, a CXCR4 antagonist, was found to inhibit both SDF-1α - induced migration and phosphorylation of ERK1/2. Investigation of cultured cells from human ATL patients revealed identical findings. Employing the SCID mouse model it could be demonstrated that AMD3100 inhibited infiltration of lymphomatous cells into liver and lung tissues in vivo. These results demonstrate the involvement of the SDF-1α /CXCR4 interaction as one mechanism of leukemic cell migration and this may provide a novel target as part of combination therapy for ATL.

ORGANISM(S): Mus musculus

PROVIDER: GSE17341 | GEO | 2009/07/28

SECONDARY ACCESSION(S): PRJNA119025

REPOSITORIES: GEO

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Transcriptional profiling of cytokines and its receptors in primary murine lymphoblastoid cells (pML cells)

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