Park Hyunkyung, Kim Hyeong-Joon, Sohn Sang-Kyun, Baik Yoonsuk, Kim Dongho, Lee Sung-Yeoun, Kong Jee Hyun, Kim Hawk, Shin Dong-Yeop, Ahn Jae-Sook, Park Jinny, Park Seonyang, Kim Inho
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Internal Medicine, Chonnam National University, Hwasun Hospital, Hwasun, Korea.
Ann Hematol. 2025 Jul 31. doi: 10.1007/s00277-025-06514-8.
The immunological mechanism of treatment-free remission is not clearly understood. We aimed to identify immune-related genetic differences that predict molecular relapse after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic phase chronic myeloid leukemia (CML). In this prospective multicenter study, patients who were treated with TKI for at least 3 years discontinued TKI and were monitored for loss of major molecular response. We used NanoString profiling to find gene expression differences associated with relapse. From August 2019 to April 2020, 42 patients were enrolled from five centers in South Korea. During the median follow-up of 16.9 months, 47.6% (20/42) of patients experienced molecular relapse. The 6- and 12-month molecular relapse-free survival (RFS) rates were 52.5% and 50%, respectively. The e14a2 transcript type and longer duration (≥ 50 months) of deep molecular response before TKI discontinuation were associated with longer molecular RFS. NanoString analysis revealed significant differences in immune-related gene expression between relapsed and non-relapsed patients at the time of TKI discontinuation, including T cell-related genes such as SIGLEC1, ARG2, CD160, and IFNG. In conclusion, differences in expression of immune-related genes may provide a prognostic marker for relapse after TKI discontinuation in patients with CML.
无需治疗即可缓解的免疫机制尚不清楚。我们旨在确定免疫相关的基因差异，以预测慢性期慢性髓性白血病（CML）患者停用酪氨酸激酶抑制剂（TKI）后分子复发的情况。在这项前瞻性多中心研究中，接受TKI治疗至少3年的患者停用TKI，并监测主要分子反应的丧失情况。我们使用NanoString分析来寻找与复发相关的基因表达差异。2019年8月至2020年4月，从韩国的五个中心招募了42名患者。在中位随访16.9个月期间，47.6%（20/42）的患者发生分子复发。6个月和12个月的分子无复发生存（RFS）率分别为52.5%和50%。e14a2转录本类型以及停用TKI前深度分子反应的持续时间更长（≥50个月）与更长的分子RFS相关。NanoString分析显示，在停用TKI时，复发患者和未复发患者之间免疫相关基因表达存在显著差异，包括SIGLEC1、ARG2、CD160和IFNG等T细胞相关基因。总之，免疫相关基因表达的差异可能为CML患者停用TKI后的复发提供预后标志物。
