2015
DOI: 10.3324/haematol.2015.135590
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Spleen tyrosine kinase inhibitors reduce CD40L-induced proliferation of chronic lymphocytic leukemia cells but not normal B cells

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Cited by 14 publications
(12 citation statements)
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“…Signaling aberrations in CLL cells may be used to guide targeted therapy. We recently showed that sCD40L stimulation more efficiently induced phosphorylation of SYK in CLL cells relative to normal B cells, and that SYK inhibitors reduced CD40L-induced proliferation of CLL cells specifically [ 22 ]. In the present study we showed that constitutive as well as induced signaling could be reversed by the use of specific pathway inhibitors.…”
Section: Discussionmentioning
confidence: 99%
“…Signaling aberrations in CLL cells may be used to guide targeted therapy. We recently showed that sCD40L stimulation more efficiently induced phosphorylation of SYK in CLL cells relative to normal B cells, and that SYK inhibitors reduced CD40L-induced proliferation of CLL cells specifically [ 22 ]. In the present study we showed that constitutive as well as induced signaling could be reversed by the use of specific pathway inhibitors.…”
Section: Discussionmentioning
confidence: 99%
“…When cells are located in their natural microenvironment they will receive signals from the microenvironment which will induce signal transduction and phosphorylation events. We have shown that activation of the CD40 co-receptor induces distinct signaling patterns in normal B cells and CLL cells 6 . To test if protein phosphorylation induced by microenvironmental stimuli is affected by cryopreservation, phospho flow was performed on fresh and cryopreserved normal B cells after exposure to sCD40L for 5–10 min.…”
Section: Resultsmentioning
confidence: 91%
“…For medium- to high-throughput screening of single cell phospho-protein levels, phospho flow cytometry is an attractive approach 2 . By applying this technique, signaling patterns have been characterized in diverse B cell malignancies 3 6 . We recently identified STAT3 (pY705) as aberrantly upregulated in a group of CLL patients and showed that STAT3 inhibitors potently kill the cancer cells 4 .…”
Section: Introductionmentioning
confidence: 99%
“…BCR signaling components such as the kinase Syk are promising drug targets in CLL [63][64][65]. Thus, we studied how BCR pathway inhibitors may impact the T h cell help of CLL cells [66]. Interestingly, we found that stimulation by CD40L activated the BCR pathway in CLL cells, including Syk and the downstream components Akt, BLNK, Btk/Itk and pErk1/2.…”
Section: Malignant T H Cell-b Cell Interaction: Chronic Lymphocytic Lmentioning
confidence: 99%