融合癌基因可以是癌症定义的分子改变，这对于诊断和治疗选择至关重要。1,2 对融合驱动的白血病（如急性早幼粒细胞白血病 (APL)、费城染色体阳性急性淋巴细胞白血病 (Ph ALL)）进行快速且易于使用的分子诊断）和慢性粒细胞白血病（CML）无法获得，这给许多医疗机构（包括社区医院和资源匮乏的环境）的及时诊断和有效的靶向治疗造成了障碍。我们使用 SHERLOCK（特异性高灵敏度酶报告解锁）开发了基于 CRISPR 的 RNA 融合转录本检测分析，用于诊断融合驱动的白血病。我们使用来自学术中心的诊断性 APL 和 CML 患者样本以及来自资源匮乏环境的干血斑验证了这些检测方法，证明了 100% 的敏感性和特异性。我们确定了检测优化，以便能够在三级癌症中心和临床实验室之外使用这些检测，从而增强该技术的潜在影响。快速护理点诊断可以通过扩大高度可治愈疾病的治疗机会来改善癌症患者的预后，否则这些疾病可能会因延迟或漏诊而导致严重的不良后果。版权所有 © 2024 美国血液学会。

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 (Ph+ ALL), and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many healthcare 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 APL and CML patient samples 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 in cancer patients by expanding access to therapies for highly treatable diseases that would otherwise lead to serious adverse outcomes due to delayed or missed diagnoses.Copyright © 2024 American Society of Hematology.