伴CBFA2T3::GLIS2融合基因的儿童急性髓系白血病临床特征及预后分析

doi:10.12372/jcp.2026.25e1170

摘要/Abstract

摘要：

目的探讨携带CBFA2T3::GLIS2融合基因的儿童急性髓系白血病（AML）患者的临床特征、治疗反应及预后。方法回顾性分析2020年6月至2023年5月我院诊治的6例CBFA2T3::GLIS2融合基因阳性儿童AML患者的临床资料，包括一般情况、临床表现、实验室检查结果、骨髓形态学、免疫分型、分子遗传学特征、治疗方案及随访结局。结果 6例患儿中，男5例、女1例，中位发病年龄16（9~19）月龄。主要临床表现为发热（5例），1例以腹痛就诊。3例合并髓外受累，FAB分型为M7型4例、M0型2例，危险分层均为高危。初诊时白细胞中位计数14.74（5.07~48.54）×10⁹/L。所有患儿均通过分子检测证实携带CBFA2T3::GLIS2融合，部分合并JAK2、NOTCH通路相关基因或ETV6变异。1例患儿化疗1疗程后于外院治疗而失访，另5例均参照CCLG-AML-2019高危组方案行诱导化疗。2个疗程后形态学完全缓解率80.0%（4/5），微小残留病灶（MRD）转阴率20.0%（1/5）。3个疗程化疗后MRD转阴率升至60.0%（3/5）；5例患儿接受同种异基因造血干细胞移植（HSCT），其中半相合移植2例，脐带血移植3例。其中移植前MRD及融合基因双阴性的3例患儿，移植后予阿扎胞苷维持治疗，截至随访终点均持续缓解，移植前MRD及融合基因阳性的2例患儿均短期内复发死亡。随访截至2025年7月，中位随访时间17（12~31）个月，2 年总生存率 60%。结论儿童AML患者伴CBFA2T3::GLIS2融合多发生于男性婴幼儿，常见M7分型，整体预后不佳。HSCT可能改善部分患儿生存，移植前MRD及融合基因定量结果是影响移植疗效的关键因素，联合去甲基化药物维持及新型靶向治疗策略或可进一步优化预后。

关键词: 急性髓系白血病, CBFA2T3::GLIS2, 儿童, 预后, 造血干细胞移植

Abstract:

Objective To investigate the clinical characteristics, treatment response, and prognosis of childhood acute myeloid leukemia (AML) with the CBFA2T3::GLIS2 fusion gene. Methods The clinical data of 6 children with CBFA2T3::GLIS2-positive AML treated at our hospital from June 2020 to May 2023 were retrospectively analyzed, including general information, clinical manifestations, laboratory results, bone marrow morphology, immunophenotype, molecular genetic features, treatment regimens, and follow-up outcomes. Results Among the 6 patients, 5 were males and 1 was female, and the median age at onset was 16 (9-19)months. Five patients presented with fever and 1 with abdominal pain. The median leukocyte count at diagnosis was 14.74 (5.07-48.54)×10⁹/L. Four cases were classified as FAB (French-American-British) M7 and 2 as M0. All patients harbored the CBFA2T3::GLIS2 fusion confirmed by molecular testing. One patient was lost to follow-up after one course of induction chemotherapy. The remaining 5 patients received high-risk induction therapy according to the CCLG-AML-2019 (China Children's Leukemia Group-AML-2019) protocol. After two cycles of induction chemotherapy, the morphological complete remission (CR) rate was 80.0% (4/5), and the minimal residual disease (MRD) negative rate was 20.0% (1/5). After three cycles of chemotherapy, the MRD negative rate increased to 60.0% (3/5). All 5 patients underwent allogeneic hematopoietic stem cell transplantation (HSCT), including 2 haploidentical and 3 umbilical cord blood transplants. Two patients relapsed and died after HSCT, while 3 remained in continuous remission. At the last follow-up, the median follow-up duration was 17 (12-31) months, and the 2-year overall survival (OS) rate was 60.0%. Conclusion AML with CBFA2T3::GLIS2 fusion in children is more common in male infants, with M7 subtype being frequent, and the overall prognosis remains unsatisfactory. Hematopoietic stem cell transplantation may improve the survival of some children, and pre-transplant MRD and fusion gene burden appear to have an important impact on transplantation outcomes. The role of demethylating agents as maintenance therapy and novel targeted strategies warrants further investigation in larger, prospective cohorts.

Key words: acute myeloid leukemia, CBFA2T3::GLIS2, child, prognosis, HSCT

中图分类号:

郭雪梅, 薛瑶, 王永韧, 戎留成, 方拥军, 林如峰. 伴CBFA2T3::GLIS2融合基因的儿童急性髓系白血病临床特征及预后分析[J]. 临床儿科杂志, 2026, 44(7): 636-643.

GUO Xuemei, XUE Yao, WANG Yongren, RONG Liucheng, FANG Yongjun, LIN Rufeng. Clinical features and prognosis of childhood acute myeloid leukemia with CBFA2T3::GLIS2 fusion[J]. Journal of Clinical Pediatrics, 2026, 44(7): 636-643.

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患儿	性别	发病年龄 /月龄	FAB 分型	免疫分型	危险分层	白细胞计数/ ×10⁹·L^-1	染色体	合并基因	乳酸脱氢酶 /U·L^-1	髓外浸润
1	男	39	M7	CD33 68.3% CD61 42.1% CD41 30% CD34 33% CD56 99.9% CD38 68.7% HLA-DR 0%	高危	6.26	46, Y,?（X; 12）（q28; q24）, del(13)(q12q14), psu dic(17;?)（13;?）, del(20)(q11.2)[9]/46, XY[11]	JAK2 变异	4 399	无
2	男	19	M0	CD33 89.4% CD34 98.5% CD117 99.8% CD56 99.2% HLA-DR 0% CD38 0%	高危	5.07	46,XY	NOCTH 变异	580	椎管占位
3	男	9	M7	CD33 98.1% CD61 10.6% CD41 11.3% CD117 99% CD56 99.8% CD38 6% HLA-DR 0%	高危	48.54	46,XY	无	2 836	无
4	男	16	M7	CD33 98.8% CD61 95.1% CD41 93.4% HLA-DR 0% CD117 36.7% CD56 96.2%	高危	32.04	46,XY	无	1 618	中枢
5	女	16	M0	CD33 97.5% CD117 99.2% CD34 97.3% CD56 98.5%	高危	15.23	无法分析	无	699	无
6	男	8	M7	CD33 97.5% CD61 58.6% CD41 82% CD34 86.2% HLA-DR 0% CD117 30.8% CD56 100%	高危	14.25	46,XY	ETV-6变异	301	软组织及骨骼

患儿	2疗后疗效	移植前状态	移植供体	预处理方案	移植后维持	随访结局	总生存期/个月
1	MRD+（0.5%）	MRD阴性，融合基因阴性	脐带血	Flu+Ara-C+Bu+Cy+CCNU（MAC）	阿扎胞苷	CR	35
2	MRD+（10%）	MRD（22%）及融合基因阳性	母亲	Dec+Bu+CCNU+Cy+Mel（MAC）	地西他滨	移植后复发，死亡	6
3	MRD+（0.25%）	MRD（0.31%）及融合基因阳性	脐带血	Dec+CCNU+Mel+Cy+Bu（MAC）	阿扎胞苷	移植后复发，死亡	11
4	MRD-	MRD阴性，融合基因阴性	姐姐	Ara-C+Flu+CCNU+Bu+TT+Cy（MAC）	阿扎胞苷	CR	31
5	-	-	-	-	-	失访	-
6	MRD+（3.75%）	MRD阴性，融合基因阴性	脐带血	Dec+CCNU+Mel+Cy+Bu+TT（MAC）	阿扎胞苷	CR	26