BACKGROUND: Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR) and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and marginal zone lymphoma (MZL) patients.
Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR), CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling.
Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p)-SFKs, p-PLCgamma, p-ERK, p-p38, p-p65 (NF-kappaB), p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCgamma levels. Impaired anti-BCR-induced p-PLCgamma was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-kappaB) was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells.
BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation-induced phosphorylation of signaling proteins in distinct cell populations can be used to identify aberrant signaling pathways.
Am old enough to understand the difference between the Bay of Pigs - and roasting a pig at a epicurian feast. Been thru the hippy, yippie and yuppie years - always remaining who I am.
Very much believe in "Sing your own song - weave your own tapestry"
Am young enough to still know the thrill of new discoveries, the beauty of the evening, to celebrate the joy of another tommorow.
Survived these many decades with a severe medical problems. Sorting out the maze of now having two lymphomas and all their nasty little companions, but I continue.
Besides, being a simple iconoclastic eclectic, have been called many things. An incurable romanticist - with a strong touch of reality. Thinker, intellectual (God, how I hate that term) - been told I am a lion with the heart of the poet.
Know how to wage war and conquer my foes - but would rather be known as one who brings hope and life. To bring hope into anothers life is the ultimate of joys.
Life should be about bringing hope, peace, vision... a sense of purpose beyond yourself.