BCR-FIBCD1-ABL1融合基因阳性的儿童慢性粒细胞白血病一例报道并文献复习

doi:10.16150/j.1671-2870.2023.05.009

摘要/Abstract

摘要：

目的：分析1例少见型BCR-ABL1融合基因阳性的慢性期慢性粒细胞白血病（chronic myelogenous leukemia, CML）儿童患者的基因表型，评价其经酪氨酸激酶抑制剂（tyrosine kinase inhibitor，TKI）治疗后的疗效，并总结数据库报道的该病以少见型融合基因e8a2 BCR-ABL1表型患者的治疗及预后。方法：分析我院收治的1例3岁的慢性期CML患者，同时检索PubMed和万方数据库中报道慢性期CML患者表现为罕见型融合基因e8a2 BCR-ABL1的情况。结果：该例患儿因皮肤瘀斑、颈部淋巴结肿大就诊于我院，骨髓细胞形态学示CML慢性期，但外周血及骨髓检查P190、P210、P230均阴性，后经外周血巢式PCR检测发现存在BCR（e8）-FIBCD1-ABL1（a2）融合基因阳性。数据库中已报道的26例e8a2型融合基因阳性的CML病例均为成人，最常见的临床表现为白细胞和血小板计数增多伴脾肿大，并以e8-ABLint1b-a2基因型为主。21例患者接受TKI治疗，其中19例（90.4%）达到不同程度的分子学反应。本例患儿亦是以白细胞升高伴血小板增多起病，在接受伊马替尼治疗后，目前持续达到完全血液学缓解，分子学无法检测到BCR-ABL1融合基因转录本，但随访至39个月时，复查见骨髓染色体呈38~40,XX,-7,-17,-20,-21,-22[cp7] /46,XX复合核型。结论：e8a2 BCR-ABL1融合基因突变所致的慢性期CML少见，本文首次报道了1例该融合基因突变所致的儿童慢性期CML病例。该患儿经TKI治疗后持续达到完全血液学缓解，但骨髓染色体发现异常核型，提示临床中该变异基因型可能发生预后不良结局，需继续密切随访患者。

关键词: 儿童, 慢性粒细胞白血病, e8a2, 酪氨酸激酶抑制剂

Abstract:

Objective: To analyze the genetic phenotype of a pediatric chronic phase chronic myeloid leukemia(CML-CP) patient with a rare BCR-ABL1 fusion transcript and evaluate the therapeutic effect of tyrosine kinase inhibitor (TKI), also we review the reported cases in the databases to explore the treatment and prognosis in chronic myeloid leukemia with e8a2 BCR-ABL1 fusion gene. Methods: A 3-year-old girl was diagnosed with CML-CP in our hospital，the laboratory results and treatment were analyzed. Treatment and response to TKI inhibitors in the CML-CP patients presented with a novel e8a2 fusion gene were reviewed by searching the databases of pubmed and wanfang. Results: The patient was admitted to our hospital due to skin ecchymosis and cervical lymph node swelling，and was diagnosed as CML by bone marrow cell morphology, but P190, P210 and P230 were negative in peripheral blood and bone marrow examination. BCR (e8) -FIBCD1-ABL1 (a2) fusion gene was positive in peripheral blood by Nested RT-PCR. A total of 26 CML patients with e8a2 BCR-ABL1 fusion transcript in the database were reviewed, all of which were adult cases. In the literature, 21 patients received TKI inhibitor treatment, 19/21 (90.4%) achieved different degrees of molecular response. This case onset with elevated white blood cells and thrombocytopenia,and after imatinib treatment， the patient had achieved complete hematologic remission, and the BCR-ABL1 fusion gene transcript could not be detected. However, the bone marrow chromosomes showed a complex karyotype of 38-40,XX,-7,-17,-20,-21,-22[cp7] /46,XX at the follow-up of 39 months. Conclusions: CMI-CP with e8a2 BCR-ABL1 genotype is rare, we first report this atypical e8a2 BCR-ABL1 transcript expression in pediatric CML patient. Although complete hematological remission continued after TKI inhibitor treatment, an abnormal karyotype was found in bone marrow chromosomes, suggesting that this variant genotype may have a poor prognosis, and following up closely is necessary.

Key words: Pediatric, Chronic myeloid leukemia, e8a2, Tyrosine kinase inhibitor

中图分类号:

R733.72
R446

张姣, 闾佳佳, 陆文丽, 张莉丹, 李卫. BCR-FIBCD1-ABL1融合基因阳性的儿童慢性粒细胞白血病一例报道并文献复习[J]. 诊断学理论与实践, 2023, 22(05): 472-479.

ZHANG Jiao, LÜ Jiajia, LU Wenli, ZHANG Lidan, LI Wei. Pediatric chronic myeloid leukemia with a BCR- FIBCD1-ABL1 fusion transcript: a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(05): 472-479.

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参考文献 29

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Case	Age	Sex	Presentation	Genotype	Therapy	Follow-up(month)	Prognosis
1^[5]	51	Male	hepatomegaly thrombocytosis	e8a2	hydroxyurea+αlpha interferon	12	PHR
2^[9]	40	Female	splenomegaly thrombocytosis	e8-ABLint1a- a2	imatinib	65	resistant
3^[10]	46	Male	leukocytosis Splenomegaly	e8-ABLint1a- a2	imatinib	3	MMR
4^[11]	25	Male	anorexia nausea	e8-BCRint8 -a2	dasatinib	3	EMR
5^[12]	51	Female	abdominal pain	e8-MAST2e2 -a2	imatinib	16	MMR
6^[13]	40	Male	leukocytosis	e8-ABLint1b -a2	imatinib	33	MMR
7^[13]	35	Male	leukocytosis	e8-ABLint1b -a2	imatinib	30	MMR
8^[13]	47	Male	leukocytosis	e8-ABLint1b -a2	imatinib	39	MMR
9-13^[14]	--	--	--	e8-ABLint1b -a2	imatinib	--	MMR
14^[14]	--	--	--	e8-DRG1e4 -a2	imatinib	--	MMR
15^[14]	--	--	--	e8-ABLint1a- a2	imatinib	--	MMR
16^[15]	43	Male	splenomegaly thrombopenia	e8-BCRint8 -a2	imatinib	12	MMR
17^[16]	55	Male	acceleration phase	e8-ABLint1b -a2	αlpha interferon	24	death
18^[17]	49	Male	fatigue、facial and palpebral conjunctiva congestion	e8a2withTP53、CDH10 mutation	dasatinib	6	MMR
19^[18]	67	Male	--	e8-PRDM12e4-a2	nilotinib / imatinib	82	DMR
20^[18]	58	Female	--	e8-SPECC1Le3-a2	imatinib	66	MMR
21^[19]	69	Female	leukocytosis	e8-ABLint1b- a2	hydroxyurea	48	no progression
22^[20]	25	Male	anorexia nausea	e8a2	dasatinib	6	MMR
23^[21]	34	Male	lymphadenopathy splenomegaly leukocytosis	e8a2	imatinib	2	extramedullary blast crisis
24^[22]	70	Male	NA	e8a2	NA	NA	NA
25^[22]	25	Female	NA	e8a2	NA	NA	NA
26^[23]	74	Male	NA	e8-ABLint1b-a2	nilotinib	12	MMR