Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience
Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience
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DOI：
10.1097/hs9.0000000000000044
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发表时间：
2018-06-01
期刊：
影响因子：
6.6
通讯作者：
Gupta, Vikas
中科院分区：
文献类型：
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作者：
Alduaij, Waleed;McNamara, Caroline J.;Gupta, Vikas
虽然新一代测序（NGS）有助于描述髓系恶性肿瘤复杂的基因组景观，但其临床应用仍不明确。这导致了NGS测试的资金不稳定，限制了其可及性。在我们的中心，作为前瞻性观察研究的一部分，使用54个基因的NGS髓系面板为所有新转诊的髓系恶性肿瘤患者提供靶向测序（TAR-SEQ）。在这里，我们评估了临床级TAR-SEQ在179例骨髓增生性肿瘤（MPN）患者的常规工作流程中的诊断、预后和潜在的治疗效用。在13例三阴性（TN） MPN患者中，缺乏JAK2、CALR和MPL驱动突变，TAR-SEQ证实8例患者存在克隆造血。在中度危性骨髓纤维化（MF）患者中，通过识别高风险（HMR）突变谱，TAR-SEQ有助于优化符合造血细胞移植（HCT）条件的患者的临床决策。在9例中危MF患者中，HMR的存在有利于HCT。缺乏HMR资料导致10例中-2风险MF患者的HCT策略延迟，其中7例在最后随访时稳定。最后，TAR-SEQ鉴定出在IDH1/2（4%）、剪接体基因（28%）和EZH2（7%）中存在各种可靶向突变的患者。其中一些患者可能是未来靶向治疗试验的潜在候选人。总之，我们已经证明，TAR-SEQ改善了TN MPN的表征，可以作为改进HCT决策的额外工具整合到临床实践中，并有可能确定未来靶向治疗试验的候选患者。
Although next-generation sequencing (NGS) has helped characterize the complex genomic landscape of myeloid malignancies, its clinical utility remains undefined. This has resulted in variable funding for NGS testing, limiting its accessibility. At our center, targeted sequencing (TAR-SEQ) using a 54-gene NGS myeloid panel is offered to all new patients referred for myeloid malignancies, as part of a prospective observational study. Here, we evaluated the diagnostic, prognostic, and potential therapeutic utility of clinical grade TAR-SEQ in the routine workflow of 179 patients with myeloproliferative neoplasms (MPN).Of 13 patients with triple negative (TN) MPN, who lacked driver mutations in JAK2, CALR, and MPL, TAR-SEQ confirmed clonal hematopoiesis in 8 patients. In patients with intermediate-risk myelofibrosis (MF), TAR-SEQ helped optimize clinical decisions in hematopoietic cell transplant (HCT)-eligible patients through identifying a high molecular risk (HMR) mutation profile. The presence of an HMR profile favored HCT in 9 patients with intermediate-1 risk MF. Absence of an HMR profile resulted in a delayed HCT strategy in 10 patients with intermediate-2 risk MF, 7 of which were stable at the last follow-up. Finally, TAR-SEQ identified patients with various targetable mutations in IDH1/2 (4%), spliceosome genes (28%), and EZH2 (7%). Some of these patients can be potential candidates for future targeted therapy trials.In conclusion, we have demonstrated that TAR-SEQ improves the characterization of TN MPN, can be integrated in clinical practice as an additional tool to refine decisionmaking in HCT, and has the potential to identify candidates for future targeted therapy trials.