Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Best Pract Res Clin Haematol. 2021 Dec;34(4):101329. doi: 10.1016/j.beha.2021.101329. Epub 2021 Oct 23.
Acute leukemias of ambiguous lineage (ALAL), including mixed phenotype acute leukemia (MPAL) and related entities such as early T-cell precursor acute leukemia (ETP-ALL), remain diagnostic and clinical challenges due to limited understanding of pathogenesis, reliance of immunophenotyping to classify disease, and the lack of a rational approach to guide selection of appropriate therapy. Recent studies utilizing genomic sequencing and complementary approaches have provided key insights that are changing the way in which such leukemias are classified, and potentially, treated. Several recurrent genomic alterations define leukemias that straddle immunophenotypic entities, such as ZNF384-rearranged childhood B-ALL and B/myeloid MPAL, and BCL11B-rearranged T/myeloid MPAL, ETP-ALL and AML. In contrast, some cases of MPAL represent canonical ALL/AML entities exhibiting lineage aberrancy. For many cases of ALAL, experimental approaches indicate lineage aberrancy arises from acquisition of a founding genetic alteration into a hematopoietic stem or progenitor cell. Determination of optimal therapeutic approach requires genomic characterization of uniformly treated ALAL patients in prospective studies, but several approaches, including kinase inhibitors and BH3 mimetics may be efficacious in subsets of ALAL.
急性双表型白血病（ALAL），包括混合表型急性白血病（MPAL）和相关实体，如早期 T 细胞前体急性白血病（ETP-ALL），由于对发病机制的认识有限、依赖免疫表型来分类疾病以及缺乏合理的方法来指导选择适当的治疗，仍然是诊断和临床挑战。最近利用基因组测序和互补方法的研究提供了关键的见解，正在改变此类白血病的分类方式，并且可能改变其治疗方式。几种反复出现的基因组改变定义了跨越免疫表型实体的白血病，例如 ZNF384 重排的儿童 B-ALL 和 B/髓系 MPAL，以及 BCL11B 重排的 T/髓系 MPAL、ETP-ALL 和 AML。相比之下，一些 MPAL 病例代表表现出谱系异常的典型 ALL/AML 实体。对于许多 ALAL 病例，实验方法表明谱系异常是由于获得一个起始的遗传改变进入造血干细胞或祖细胞。确定最佳治疗方法需要在前瞻性研究中对经过统一治疗的 ALAL 患者进行基因组特征分析，但包括激酶抑制剂和 BH3 模拟物在内的几种方法可能对 ALAL 的某些亚组有效。
