Department of Pathology, UT Southwestern Medical Center, USA.
Department of Pathology, Perelman School of Medicine, Hospital of the University of Pennsylvania, USA.
Leuk Res. 2023 Jul;130:107309. doi: 10.1016/j.leukres.2023.107309. Epub 2023 May 10.
Mixed phenotype acute leukemia (MPAL) is a heterogenous group of acute leukemias characterized by leukemic blasts that express markers of multiple lineages. The revised 4th edition WHO classification of MPAL excludes AML with myelodysplasia related changes (AML-MRC), including those with complex karyotype (CK), from a diagnosis of MPAL. Abnormal karyotype is frequent in MPAL with the reported rate of CK in MPAL ranging from 19% to 32%. Due its rarity, the clinical and genetic features of MPAL with CK remain poorly characterized. This study aims to further characterize the genetic features of MPAL with CK in comparison to cases of AML and ALL with CK. Cases of de novo MPAL, AML, and B- and T-ALL patients with CK were collected from 8 member institutions of the Bone Marrow Pathology Group. We found no significant difference in overall survival between MPAL with CK compared to AML and ALL with CK. AML with CK was more strongly associated with TP53 mutations, however the presence of TP53 mutations conferred a worse prognosis regardless of lineage. ALL with CK seems to show increased IKZF1 mutation rates which is known to confer a worse prognosis in ALL. Additionally, MPAL with CK showed similarly poor outcomes regardless of whether a lymphoid or myeloid chemotherapy regimen is chosen. Our results suggest that acute leukemias with complex karyotype show a similarly poor outcome regardless of lineage differentiation and that mutation in TP53 confers a poor prognosis in all lineages. Our results support the exclusion of immunophenotypic MPAL with CK from MPAL and appear to confirm the approach proposed in the revised 4th edition WHO to include them as AML with myelodysplasia-related changes and similar myelodysplasia-related AML categories of newer classifications.
混合表型急性白血病（MPAL）是一组异质性急性白血病，其特征为表达多个谱系标志物的白血病细胞。修订后的第 4 版世界卫生组织（WHO）分类法将伴有伴髓系发育异常相关改变的急性髓系白血病（AML-MRC），包括具有复杂核型（CK）的病例，排除在 MPAL 诊断之外。MPAL 中异常核型较为常见，CK 在 MPAL 中的报告率为 19%至 32%。由于其罕见性，CK 型 MPAL 的临床和遗传特征仍未得到充分描述。本研究旨在通过与 CK 型 AML 和 ALL 病例相比，进一步描述 CK 型 MPAL 的遗传特征。从 8 个骨髓病理学组（Bone Marrow Pathology Group）成员机构收集了初发的 MPAL、AML 和 B 细胞及 T 细胞 ALL 患者伴 CK 的病例。我们发现 CK 型 MPAL 与 AML 和 ALL 相比，总生存率没有显著差异。CK 型 AML 与 TP53 突变的相关性更强，然而，无论谱系如何，TP53 突变的存在均预示着预后更差。CK 型 ALL 似乎显示出 IKZF1 突变率增加，这在 ALL 中已知预示着预后更差。此外，无论选择何种淋巴系或髓系化疗方案，CK 型 MPAL 的结果均较差。我们的结果表明，具有复杂核型的急性白血病无论分化谱系如何，均显示出相似的不良结局，而 TP53 突变在所有谱系中均预示着预后不良。我们的结果支持将 CK 型免疫表型 MPAL 排除在 MPAL 之外，并似乎证实了在修订后的第 4 版 WHO 中的方法，即将其纳入伴有伴髓系发育异常相关改变的 AML 和较新分类中的类似髓系发育异常相关 AML 类别。
