Hirabayashi Shinsuke, Manabe Atsushi, Ohki Kentaro, Kiyokawa Nobutaka
Department of Pediatrics, Hokkaido University Graduate School of Medcine.
Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development.
Rinsho Ketsueki. 2023;64(7):633-638. doi: 10.11406/rinketsu.64.633.
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has many subtypes with diverse clinical and biological features and outcomes. Next generation sequencing has revealed several novel subtypes, including the ZNF384 and MEF2D rearrangements. The clinical characteristics and outcomes of the largest series of BCP-ALL cases with ZNF384 and MEF2D rearrangements in an international collaborative study are described here. Patients with ZNF384 rearrangements appear to express various leukemic phenotypes, including BCP-ALL (with or without abnormal expression of myeloid markers) and B/myeloid mixed phenotype acute leukemia. We provide strong evidence that among BCP-ALL patients with a ZNF384 fusion, the partner gene is associated with demographic features and influences the outcome; particularly the EP300-ZNF384 fusion is associated with a low risk of relapse. MEF2D rearrangements have been primarily described in children and young adults with BCP-ALL. Previous research has suggested that patients with MEF2D-BCL9 fusion have a high risk of relapse. Despite having the MEF2D-HNRNPUL1 fusion gene, the prognosis was favorable. Improved diagnostic genomic testing will enable future prospective studies to clarify the clinical significance of the ZNF384 and MEF2D rearrangements in childhood and young adult BCP-ALL.
B细胞前体急性淋巴细胞白血病（BCP-ALL）有许多具有不同临床、生物学特征及预后的亚型。新一代测序已揭示了几种新亚型，包括ZNF384和MEF2D重排。本文描述了一项国际合作研究中最大系列的伴有ZNF384和MEF2D重排的BCP-ALL病例的临床特征及预后。伴有ZNF384重排的患者似乎表现出各种白血病表型，包括BCP-ALL（有或无髓系标志物异常表达）及B/髓系混合表型急性白血病。我们提供了强有力的证据，表明在伴有ZNF384融合的BCP-ALL患者中，伙伴基因与人口统计学特征相关并影响预后；特别是EP300-ZNF384融合与低复发风险相关。MEF2D重排主要在患有BCP-ALL的儿童和年轻人中被描述。先前的研究表明，伴有MEF2D-BCL9融合的患者有高复发风险。尽管存在MEF2D-HNRNPUL1融合基因，但其预后良好。改进的诊断性基因组检测将使未来的前瞻性研究能够阐明ZNF384和MEF2D重排在儿童和年轻成人BCP-ALL中的临床意义。
