Plasma proteomics in CML patients before and after initiation of tyrosine kinase inhibitor therapy reveals induced Th1 immunity and loss of angiogenic stimuli

Small pilot study to evaluate use of multiplex plasma protein analysis in clinical studies of chronic myeloid leukemia (CML). Used Proseek, RBM and Mesoscale to look at 124 analytes in total (not to compare between platforms, but to maximize number of analytes). Patients were treated with standard tyrosine kinase inhibitors and samples taken before, and 3 months after treatment began. Most CML patients have excellent long-term prognosis with these drugs, but a few develop resistance and/or serious side effects, and biomarkers giving insights into these issues would be useful. Looked at just 14 patients, 9 treated with imatinib and 5 with dasatinib and examined with Proseek Onc I, the MesoScale human proinflammatory (9-plex) kit and RBM’s custom human MAP (44-plex) – data showing treatment-related changes in relative levels from all three platforms was extrapolated together in this explorative study. Results for overlapping analytes were mostly in agreement, and those that differed were generally at very low levels in plasma and “close to the platform’s limits of detection”. For cytokines/chemokines etc, Th1-promoting (anti-tumorigenic) proteins tended to be upregulated after treatment, whereas Th2-promoting (pro-tumorigenic) markers were downregulated. Several pro-angiogenic proteins were also significantly downregulated post-treatment. These patterns were very much “as expected” in terms of biological expectations for response to treatment. A few less-predictable proteins also showed significance, and the authors considered that CA9, GH and uPAR were all of interest for further investigation as potentially useful markers for clincal studies of CML.