Abstract：
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.
摘要：
混合表型急性白血病（MPAL）是一组异质性的急性白血病，其特征是白血病母细胞表达多个谱系的标志物。世卫组织修订的第4版MPAL分类排除了AML伴骨髓增生异常相关变化（AML-MRC），包括那些具有复杂核型（CK），从MPAL的诊断。MPAL中异常核型常见，据报道MPAL中CK的发生率为19％至32％。由于它的稀有性，MPAL伴CK的临床和遗传特征仍未明确。本研究旨在与AML和ALL伴CK的病例相比，进一步表征MPAL伴CK的遗传特征。从头MPAL病例，AML,从骨髓病理学组的8个成员机构收集了CK的B和T-ALL患者。我们发现，与AML和ALL与CK相比，MPAL与CK之间的总体生存率没有显着差异。有CK的AML与TP53突变密切相关，然而,无论谱系如何,TP53突变的存在都会导致更差的预后.具有CK的ALL似乎显示出增加的IKZF1突变率,已知这在ALL中赋予更差的预后。此外,无论选择淋巴或髓样化疗方案，带有CK的MPAL都显示出类似的不良结局。我们的结果表明，无论谱系分化如何，具有复杂核型的急性白血病均表现出类似的不良结局，并且TP53的突变在所有谱系中均导致不良预后。我们的结果支持从MPAL中排除具有CK的免疫表型MPAL，并且似乎证实了WHO修订版第4版中提出的方法，该方法将其纳入具有骨髓增生异常相关变化的AML和类似的骨髓增生异常相关AML类别的新分类。
