In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 46.9-46.9
Abstract:
Human SLAMF1 (CD150) is expressed on T, B, NK, and dendritic cells where it acts as a co-activator through self interactions. Gene expression profiling has identified SLAMF1 as part of the genetic signature characterizing chronic lymphocytic leukemia (CLL) patients with favorable prognosis. The analysis of SLAMF1 expression on the CD19+ fraction of 220 patients with CLL revealed highly variable levels. Statistical analyses indicate that patients characterized by a good prognosis express higher levels of SLAMF1 compared to the counterpart. Furthermore, patients with less than 6% SLAMF1+/CD19+ CLL cells had a significantly longer treatment free survival (median 6.4 in SLAMF1- vs 1.2 years in SLAMF1+ patients, P=.002). SLAMF1 expression was also inversely correlated with CD38, CD49d and ZAP-70, and positively associated with the presence of somatic mutations in the IgHV genes, all molecular hallmarks of good prognosis. Incubation of CLL cells with anti-SLAMF1 mAb induced a robust tyrosine phosphorylation pattern, mediated by the EAT-2 adaptor. Activated intracellular molecules included lyn, vav-1, p38 and jnk. Co-crosslinking of SLAMF1 with sIgM prolonged phosphorylation of p38 and jnk and increased the percentage of CLL cells undergoing apoptosis, as compared to either signal alone. In conclusion, SLAMF1 represents a novel marker for CLL patients with a favorable prognosis. Functional data suggest that it may function together with the BCR in regulating CLL apoptosis.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.46.9
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
