Zheng Ruifang, Gagan Jeffrey R, Botten Giovanni A, Koduru Prasad, Weinberg Olga K, Chen Mingyi, Cantu Miguel D, Jaso Jesse, Germans Sharon, Luu Hung S, Han Lina, Slone Tamra L, Dickerson Kathryn E, John Samuel, Madanat Yazan F, Chung Stephen, Collins Robert, Marinos Alejandro, Fuda Franklin, Chen Weina
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Eur J Haematol. 2025 Jun;114(6):1041-1051. doi: 10.1111/ejh.14414. Epub 2025 Mar 18.
Mixed phenotype acute leukemia (MPAL) often poses challenges in diagnosis and clinical management. This is the first study to assess the lineage/immunophenotype-genotype association and the significance of AML-myelodysplasia-related changes (MR, cytogenetic abnormalities and gene mutations, AML-MR-CG-Gene) in MPAL classification.
We conducted a clinicopathologic and genomic evaluation of 25 MPAL cases by the WHO-HEM5/ICC classification criteria, except for retaining those MPAL cases with AML-MR-CG-Gene (Conditional-MPAL).
The majority of MPAL cases (22/25, 88%) showed distinct genotypes that overlapped with those of lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The genomic profile of ALL-like and AML-like was associated with immunophenotypically lymphoid and myeloid lineage predominance, respectively. The lineage/immunophenotype-genotype association may provide a rationale to develop a lineage-immunophenotypically/biologically guided therapy selection. Additionally, 64% of MPAL cases carried AML-MR-CG-Gene, half of which were MPAL with lymphoid-lineage predominance and had ALL-like molecular signatures, and most of these patients responded well to the ALL-based induction regimens. These results support that Conditional-MPAL with AML-MR-CG-Gene may be better diagnosed as MPAL rather than AML-MR.
Genomic landscape of AML-like or ALL-like MPAL is associated with the immunophenotypic lineage predominance, and such association could impact treatment decisions and provide supporting evidence to refine MPAL diagnostic criteria in future studies.
混合表型急性白血病（MPAL）在诊断和临床管理中常常带来挑战。这是第一项评估谱系/免疫表型-基因型关联以及AML-骨髓增生异常相关改变（MR、细胞遗传学异常和基因突变，AML-MR-CG-Gene）在MPAL分类中的意义的研究。
我们根据WHO-HEM5/ICC分类标准对25例MPAL病例进行了临床病理和基因组评估，但保留了那些具有AML-MR-CG-Gene的MPAL病例（条件性MPAL）。
大多数MPAL病例（22/25，88%）显示出与淋巴细胞白血病（ALL）和急性髓系白血病（AML）重叠的独特基因型。ALL样和AML样的基因组谱分别与免疫表型上的淋巴系和髓系优势相关。谱系/免疫表型-基因型关联可能为制定谱系免疫表型/生物学指导的治疗选择提供理论依据。此外，64%的MPAL病例携带AML-MR-CG-Gene，其中一半是淋巴系优势的MPAL，具有ALL样分子特征，并且这些患者中的大多数对基于ALL的诱导方案反应良好。这些结果支持，具有AML-MR-CG-Gene的条件性MPAL可能更好地诊断为MPAL而非AML-MR。
AML样或ALL样MPAL的基因组格局与免疫表型谱系优势相关，这种关联可能影响治疗决策，并为未来研究完善MPAL诊断标准提供支持证据。
