CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.

Autor:	Vedula RS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Karp HQ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Koob J; Broad Institute of MIT and Harvard, Cambridge, MA., Lim F; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Garcia JS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Winer ES; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Luskin MR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Ghiaur G; Johns Hopkins Medical Institute, Baltimore, MD., Kim AS; Department of Pathology, Brigham and Women's Hospital, Boston, MA., Beppu LW; Fred Hutchinson Cancer Center, Seattle, WA., Sala-Torra O; Fred Hutchinson Cancer Center, Seattle, WA., Radich J; Fred Hutchinson Cancer Center, Seattle, WA., Gootenberg J; McGovern Institute, Cambridge, MA., Abudayyeh O; McGovern Institute, Cambridge, MA., Zhang F; Broad Institute of MIT and Harvard, Cambridge, MA., Lindsley RC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Sep 19; Vol. 144 (12), pp. 1290-1299.
DOI:	10.1182/blood.2023022908
Abstrakt:	Abstract: Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia, and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many health care settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) for the diagnosis of fusion-driven leukemias. We validated these assays using diagnostic samples from patients with APL and CML from academic centers and dried blood spots from low-resource environments, demonstrating 100% sensitivity and specificity. We identified assay optimizations to enable the use of these tests outside of tertiary cancer centers and clinical laboratories, enhancing the potential impact of this technology. Rapid point-of-care diagnostics can improve outcomes for patients with cancer by expanding access to therapies for highly treatable diseases that would otherwise lead to serious adverse outcomes due to delayed or missed diagnoses. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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