Shi Sophia, Zhou Qianghua, Zhao Davidson, Zarif Mojgan, Wei Cuihong, Sibai Hassan, Chang Hong
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Hematology, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Leuk Res. 2025 Apr;151:107665. doi: 10.1016/j.leukres.2025.107665. Epub 2025 Feb 18.
Mixed-phenotype acute leukemia with BCR::ABL1 fusion (MPAL), previously known as Philadelphia chromosome-positive mixed phenotype acute leukemia, is a heterogeneous group that is segregated into different subtypes based on WHO-HAEM5. The genetic profile of MPAL remains poorly defined due to its rarity.
We conducted a retrospective study of 16 patients with MPAL and compared their clinical and laboratory profiles to 20 patients with AML.
Compared to patients with AML with a median age of 64 years old, patients with MPAL were significantly younger at a median of 47 years old (P = 0.031) with similar white blood cell (WBC) count, hemoglobin (Hb) count, platelet (PLT) count, lactate dehydrogenase (LDH) levels, and bone marrow blast percentage. MPAL patients harboured a similar frequency of co-occurring additional cytogenetic abnormalities (ACA) compared to AML with monosomy 7 (25 %) being the most common ACA in MPAL. The most commonly mutated gene in MPAL patients was RUNX1 at 45 %. The overall survival (OS) and event-free survival (EFS) between MPAL and AML significantly differed, conferring a better prognosis for patients with MPAL.
Our results indicate that adult patients with MPAL present with younger age and may have better survival outcomes than patients with AML. In addition, our next-generation sequencing (NGS) data indicates that RUNX1 is frequently mutated in B/myeloid MPAL compared to AML. Future studies are warranted to further elucidate the role of RUNX1 in this disease.
伴有BCR::ABL1融合的混合表型急性白血病（MPAL），以前称为费城染色体阳性混合表型急性白血病，是一个异质性群体，根据世界卫生组织血液肿瘤分类第5版（WHO-HAEM5）分为不同亚型。由于其罕见性，MPAL的基因特征仍不清楚。
我们对16例MPAL患者进行了回顾性研究，并将他们的临床和实验室特征与20例急性髓系白血病（AML）患者进行了比较。
与中位年龄为64岁的AML患者相比，MPAL患者明显年轻，中位年龄为47岁（P = 0.031），白细胞（WBC）计数、血红蛋白（Hb）计数、血小板（PLT）计数、乳酸脱氢酶（LDH）水平和骨髓原始细胞百分比相似。与伴有7号染色体单体的AML相比，MPAL患者同时出现其他细胞遗传学异常（ACA）的频率相似，7号染色体单体是MPAL中最常见的ACA。MPAL患者中最常发生突变的基因是RUNX1，突变率为45%。MPAL和AML之间的总生存期（OS）和无事件生存期（EFS）有显著差异，MPAL患者的预后较好。
我们的结果表明，成年MPAL患者年龄较轻，与AML患者相比可能有更好的生存结果。此外，我们的二代测序（NGS）数据表明，与AML相比，RUNX1在B/髓系MPAL中经常发生突变。未来有必要进行进一步研究，以阐明RUNX1在这种疾病中的作用。
