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Status |
Public on Mar 03, 2009 |
Title |
CLL: CD38+CD49d+ vs. CD38-CD49d- |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
CD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ vs. CD38-CD49d- CLL cells, we demonstrated overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also upregulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38-CD49d- cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors for CCL3 and CCL4, were found in CLL-derived monocyte-macrophages. Consistently, CCL3 increased monocyte migration, and CD68+ macrophage infiltration was particularly high in BMB from CD38+CD49d+ CLL. Conditioned media from CCL3-stimulated macrophages induced endothelial cells to express VCAM-1, the CD49d ligand, likely through TNFα over-production. These effects were apparent in BMB from CD38+CD49d+CLL, where lymphoid infiltrates were characterized by a prominent meshwork of VCAM-1+ stromal/endothelial cells. Lastly, CD49d engagement by VCAM-1-transfectants increased viability of CD38+CD49d+ CLL cells. Altogether, CD38 and CD49d can be thought of as a part of a consecutive chain of events ultimately leading to improved survival of CLL cells.
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Overall design |
Dual Color reference design with 26 different patients (15 cd38-cd49d- and 11 cd38+cd49d+)
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Contributor(s) |
Zucchetto A, Benedetti D, Tripolo C, Bomben R, Dal Bo M, Marconi D, Gattei V, Gaidano G, Deagan M, Malavasi F, Lorenzon D, Rossi FM, Rossi D, Bulian P, Franco V, Del Poeta G, Tedesco F |
Citation missing |
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Submission date |
Jan 25, 2009 |
Last update date |
Feb 22, 2018 |
Contact name |
daniela marconi |
E-mail(s) |
daniela.marconi@gmail.com
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Organization name |
CRO AVIANO
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Street address |
Via franco Gallini 2
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City |
Aviano |
ZIP/Postal code |
33081 |
Country |
Italy |
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Platforms (1) |
GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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Samples (26)
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Relations |
BioProject |
PRJNA111739 |
Supplementary file |
Size |
Download |
File type/resource |
GSE14560_RAW.tar |
350.1 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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