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Identification of potential of new therapeutic approaches for JAK2 V617F mutant patients

ABSTRACT: n patients with PMF, excessive secretion of inflammatory cytokines results in fibrotic changes in bone marrow and diminishes the quality of life of the affected patients due to systemic symptoms long-term ruxolitinib therapy may reverse or markedly delay BM fibrosis progression in advanced MF suggests kavasincha 2018

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Bethany Geary

LAB HEAD: Bethany Geary

PROVIDER: PXD027250 | Pride | 2023-05-18

REPOSITORIES: Pride

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Project description:TARGET (Tumour characterisation to Guide Experimental Targeted therapy) seeks to optimise the pathway for molecular characterisation of all patients entering early phase cancer trials to inform clinical decision-making on optimal therapy. Performance status (PS) was developed to assess a patient’s ability to perform a variety of activities to further inform clinical decision making on optimal therapy including appropriate inclusion in clinical trials. However, the quality of present algorithms to assess performance status are limited and based on a semi-quantitative clinician assessment. In particular, a common eligibility criterion for entry into early phase cancer clinical trials is a life expectancy of >3 or 6 months. Here we investigate proteomics as a means of more objective and quantitative assessment of both performance status and thus likely prognosis prior to clinical trial enrolment. Improved patient stratification at enrolment would reduce the number of patients unnecessarily exposed to potentially toxic drugs and decrease withdrawal from trials. Plasma samples from patients enrolled into the TARGET trial were analysed using the mass spectrometry (MS) technique: Sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS. SWATH-MS was used on a discovery cohort of 73 patients to identify proteins that could differentiate patients into either a good or poor prognosis. A three-protein panel showed a stronger prediction of overall survival (p = 0.000086) compared to PS (p = 0.001). This panel was then tested against a validation cohort of 77 patients. The panel was determined as being a significant (p = 0.000451) predictor of overall survival whereas PS was not significant. The panel had a receiver operating characteristic curve area under the curve (AUC) of 0.73 in the validation set; the AUC of PS was 0.54. This signature can now be developed further in larger patient populations to assess its utility in a clinical setting.

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Identification of potential of new therapeutic approaches for JAK2 V617F mutant patients

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