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  • Title: Relatively favorable prognosis for MLL-rearranged childhood acute leukemia with reciprocal translocations.
    Author: Yang L, Ding L, Liang J, Chen J, Tang Y, Xue H, Gu L, Shen S, Li B, Chen J.
    Journal: Pediatr Blood Cancer; 2018 Oct; 65(10):e27266. PubMed ID: 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.
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