The Proteogenomic Translational Research Center for acute myelogenous leukemia, or AML, is focused on three substantial, unmet clinical needs associated with the disease: 1) identifying the most effective first-line targeted therapeutic; 2) characterizing the interaction between multiple therapies, particularly tyrosine kinase inhibitors (TKIs), other small molecule inhibitors, and induction chemotherapy; and 3) identifying the most effective second round therapy following relapse of initial TKI therapy.
The team plans to address these clinical needs by using proteomics capabilities at PNNL, including significantly improved approaches for ultrasensitive targeted proteomics and increased throughput and depth of coverage in global discovery proteomics. A combination of isobaric labeling and extensive fractionation will be used to provide deep quantitative proteomic and phosphoproteomic coverage in preclinical model systems based on primary patient-derived AML cells exposed to TKIs and other small molecule inhibitors ex vivo. In parallel, ultrasensitive targeted proteomics will be used to test the resulting signatures in clinical model systems based on primary cells obtained from AML patients before and after treatment in National Cancer Institute-sponsored clinical trials of targeted inhibitors, alone or in combination, with standard of care induction chemotherapy.
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