Dissertation committee:
Κλεονίκη Λάμνησου Αναπληρώτρια Καθηγήτρια Επιβλέπουσα, Βασιλική Αλεπόρου-Μαρίνου Αναπληρώτρια Καθηγήτρια, Παναγούλα Κόλλια Επίκουρη καθηγήτρια
Summary:
The available data on Toll-like receptors (TLRs) expression in chronic
lymphocytic leukemia (CLL) are limited and derive from small series of
patients. We profiled the expression of TLR signaling pathway-associated genes
in 192 CLL cases and explored potential associations with molecular features of
the B cell receptor (BcR). CLL cells express all TLRs expressed by activated B
cells, with high expression of TLR7 and CD180, intermediate of TLR1, TLR6,
TLR10 and low of TLR2 and TLR9. The vast majority of adaptors, effectors and
members of the NF-KB, JNK/p38, NF/IL6 and IRF pathways are
intermediately-to-highly expressed, while inhibitors of TLRs activity are
generally low-to-undetectable, indicating that the TLR signaling framework is
competent in CLL. Significant differences were identified for selected genes
between cases carrying mutated vs. unmutated IGHV genes or assigned to
different subsets with stereotyped BcRs. The differentially expressed molecules
include receptors, NFκB/MAPK signaling molecules and final targets of the
cascade. The observed variations are suggestive of distinctive activation
patterns of the TLR signaling pathway in subgroups of CLL cases defined by BcR
molecular features, and indicate that different or concomitant signals acting
through receptors other than the BcR can affect the behavior of the malignant
clone.
Keywords:
Chronic lymphocytic leukemia (CLL), Toll-like receptors (TLRs), Antigenic stimulation, B-cell receptor, Stereotypy