@misc{10481/110283,
year = {2025},
month = {10},
url = {https://hdl.handle.net/10481/110283},
abstract = {Multiple myeloma (MM) is a plasma cell neoplasm characterized by high inter- and intra-patient clonal heterogeneity, leading to high variability in therapeutic responses. Minimally invasive biomarkers that predict response may help personalize treatment decisions. IsoSeek, a single-nucleotide resolution small RNA sequencing method can profile thousands of microRNAs (miRNAs) and their variants (isomiRs) from patient plasma-purified extracellular vesicles (EVs). Machine learning-generated miRNA/isomiR classifiers accurately predict therapeutic response in relapsed/refractory MM (RRMM) patients receiving daratumumab-containing regimens, achieving an area-under-the-curve of 0.98 (95% confidence interval [CI]:0.94–1.00). A classifier signature with the plasma cell-selective miR-148-3p, predicts durable response (≥6 months), progression-free (hazard ratio [HR]: 33.09, 95% CI: 4.2–262, p < 0.001), and overall survival (HR: 3.81, 95% CI: 1.05–13.99, p < 0.05). Targetome analysis connects the prognostic classifier to established MM drug targets BCL2 and MYC suggesting biological relevance. Thus, EV-isomiR sequencing in MM patients offers a tumor-naïve alternative to an invasive bone-marrow biopsy for predicting treatment outcome.},
organization = {Stichting Cancer Center Amsterdam (CCA2021-9-77, CCA2023-9-93)},
organization = {Spanish Government (AGL2017-88702-C2-2-R)},
organization = {NWO Perspectief Cancer-ID, TKI-health Holland AQrate, Stichting NEXTGEN HIGHTECH Program},
publisher = {Elsevier},
keywords = {multiple myeloma},
keywords = {liquid biopsy},
keywords = {extracellular vesicles},
keywords = {miRNAs},
keywords = {isomiR modelling},
keywords = {response prediction},
keywords = {personalized therapy},
title = {Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma},
doi = {10.1016/j.xcrm.2025.102358},
author = {Gómez Martín, Cristina and Drees, Esther E. E. and Van Eijndhoven, Monique A. J. and Groenewegen, Nils and Wang, Steven and Verkuijlen, Sandra AWM and Van Weering, Jan R. T. and Aparicio-Puerta, Ernesto and Bosch, Leontien and Frerichs, Kris A. and Verkleij, Christie P. M. and Kersten, Marie J. and Zijlstra, Josée M. and De Jong, Daphne and Groothuis-Oudshoorn, Catharina G. M. and Hackenberg, Michael and Pegtel, D. Michiel},
}