伴有相互易位的 MLL 重排儿童急性白血病具有相对有利的预后。

Relatively favorable prognosis for MLL-rearranged childhood acute leukemia with reciprocal translocations.

机构信息

Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Pediatr Blood Cancer. 2018 Oct;65(10):e27266. doi: 10.1002/pbc.27266. Epub 2018 Jun 26.

DOI:10.1002/pbc.27266

PMID:29943896

Abstract

BACKGROUND

Mixed-lineage leukemia (MLL) with multifarious partner genes leads to aggressive leukemia with dismal outcomes.

METHODS

Using panel-based targeted sequencing, we examined 90 cases with MLL-rearranged (MLL-r) childhood acute leukemia, including 55 with acute lymphoblastic leukemia (ALL) and 35 with acute myeloid leukemia (AML).

RESULTS

MLL breakpoints and complete rearrangements were identified. A total of 37.8% (34/90) of patients displayed a single direct MLL fusion gene, 15.6% (14/90) carried a single reciprocal fusion, and 27.8% (25/90) had both reciprocal MLL fusion alleles. The remaining 17 MLL-r cases exhibited complex translocations with homozygous disruptions on chromosome 11 or two breakpoints on the same MLL allele with a deletion of functional regions. A total of 77 patients (45 ALL and 32 AML) received chemotherapy with a median follow-up of 2.5 years. Unexpectedly, we identified children with reciprocal MLL fusions who exhibited relatively favorable outcomes compared with those in children with complex translocations or a single direct MLL fusion allele (66.1% vs. 24.6% and 27.6%, P = 0.001). Reciprocal MLL fusion may be functionally rescued by a partially truncated MLL protein.

CONCLUSION

Comprehensive MLL-r analysis by targeted next-generation sequencing can provide detailed molecular information and is helpful for precise stratified treatment and clinical prognosis determination.

摘要

背景

混合谱系白血病（MLL）与多种伙伴基因融合导致侵袭性白血病，预后不良。

方法

我们采用基于panel 的靶向测序方法，检测了 90 例 MLL 重排（MLL-r）儿童急性白血病病例，包括 55 例急性淋巴细胞白血病（ALL）和 35 例急性髓系白血病（AML）。

结果

鉴定了 MLL 断点和完全重排。共有 37.8%（34/90）的患者存在单一的直接 MLL 融合基因，15.6%（14/90）携带单一的相互融合基因，27.8%（25/90）同时存在相互 MLL 融合等位基因。其余 17 例 MLL-r 病例表现为复杂易位，11 号染色体纯合缺失或同一 MLL 等位基因上存在两个断点并伴有功能区缺失。77 例（45 例 ALL 和 32 例 AML）患者接受了化疗，中位随访时间为 2.5 年。出乎意料的是，我们发现相互 MLL 融合的患儿与复杂易位或单一直接 MLL 融合等位基因的患儿相比，预后相对较好（66.1%比 24.6%和 27.6%，P=0.001）。部分截断的 MLL 蛋白可能对相互 MLL 融合具有功能拯救作用。