ZNF384 fusion transcript levels for measurable residual disease monitoring in adult B-cell acute lymphoblastic leukemia

IF 3.3 4区 医学 Q2 HEMATOLOGY
Zong-Yan Shi, Xu Wang, Wen-Min Chen, Ling-Di Li, Yue Hao, Jin-Ying Li, Kai Sun, Xiao-Su Zhao, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin
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Abstract

Zinc finger protein 384 (ZNF384) rearrangement defined a novel subtype of B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of ZNF384 fusion transcript levels represented measurable residual disease remains to be explored. ZNF384 fusions were screened out in 57 adult B-ALL patients at diagnosis by real-time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of ZNF384 fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5-log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (p = 0.022 and = 0.0083) and course 2 consolidation (p = 0.0025 and = 0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS of patients with <2.5-log reduction after course 1 consolidation (p < 0.0001 and = 0.0002) and course 2 consolidation (p = 0.0003 and = 0.019), whereas exerted no significant effects in patients with ≥2.5-log reduction (all p > 0.05). ZNF384 fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo-HSCT in adult B-ALL.

监测成人 B 细胞急性淋巴细胞白血病中可测量残留疾病的 ZNF384 融合转录本水平
锌指蛋白384(ZNF384)重排定义了B细胞急性淋巴细胞白血病(B-ALL)的一种新亚型。ZNF384融合转录本水平代表可测量残留疾病的预后意义仍有待探索。通过实时定量聚合酶链反应筛选出了57名成年B-ALL患者诊断时的ZNF384融合,并在治疗过程中连续监测其转录本水平。完全缓解时ZNF384融合转录本水平的降低对生存无显著影响,而其≥2.5-log的降低与第1疗程巩固治疗(p = 0.022和= 0.0083)和第2疗程巩固治疗(p = 0.0025和= 0.0008)后较高的无复发生存率(RFS)和总生存率(OS)显著相关。与单纯化疗相比,异基因造血干细胞移植(allo-HSCT)可明显改善第一疗程巩固治疗后(p < 0.0001和= 0.0002)和第二疗程巩固治疗后(p = 0.0003和= 0.019)<2.5-log降低的患者的RFS和OS,而对≥2.5-log降低的患者无明显效果(均为p >0.05)。第1疗程和第2疗程巩固治疗后的ZNF384融合转录本水平可有力预测复发和生存率,并可为成人B-ALL患者是否接受allo-HSCT提供指导。
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来源期刊
Hematological Oncology
Hematological Oncology 医学-血液学
CiteScore
4.20
自引率
6.10%
发文量
147
审稿时长
>12 weeks
期刊介绍: Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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