Topoisomerase I-DNA Covalent Complexes in Myeloid Malignancies: A Potential Biomarker for Topoisomerase I Inhibitor Sensitivity

Conclusions: Based on recent clinical results, there has been renewed interested in topoisomerase I inhibitors, especially for aggressive and transformed MPNs. Topoisomerase I-DNA complex repair/downregulation has been a hallmark of drug resistance to topoisomerase I inhibitors. Therefore, detecting and quantifying these complexes in treated samples has been hypothesized to provide insight into the drug sensitivity, which is particularly important in camptothecins and platinating agents given their narrow therapeutic windows. Immunodetection techniques using an anti-TopIcc antibody may help predict sensitivity of AML to topoisomerase I inhibitors and will be used as a correlative biomarker study in an upcoming phase II randomized study of topotecan/carboplatin with or without veliparib or placebo in advanced myeloproliferative disorders and chronic myelomonocytic leukemia (ClinicalTrials.gov NCT03289910).DisclosuresPratz: AbbVie: Consultancy, Research Funding; Agios: Research Funding; Astellas: Consultancy, Research Funding; Boston Scientific: Consultancy; Millenium/Takeda: Research Funding. Kaufmann: Mayo Clinic: Patents & Royalties: Co-inventor on a patent held by Mayo Clinic for the use of the anti-TOP1cc antibody as a diagnostic reagent.

Source: Blood - November 21, 2018 Category: Hematology Authors: Kohorst, M. A., Flatten, K. S., Peterson, K. L., Schneider, P. A., Correia, C., Pratz, K. W., Smith, B. D., Kaufmann, S. H. Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases Source Type: research