Molecular genetic characterization of mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion

Mixed-phenotype acute leukemia with BCR::ABL1 fusion (MPAL^BCR::ABL1), 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^BCR::ABL1 remains poorly defined due to its rarity.

We conducted a retrospective study of 16 patients with MPAL^BCR::ABL1 and compared their clinical and laboratory profiles to 20 patients with AML^BCR::ABL1.

Compared to patients with AML^BCR::ABL with a median age of 64 years old, patients with MPAL^BCR::ABL1 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^BCR::ABL1 patients harboured a similar frequency of co-occurring additional cytogenetic abnormalities (ACA) compared to AML^BCR::ABL1 with monosomy 7 (25 %) being the most common ACA in MPAL^BCR::ABL1. The most commonly mutated gene in MPAL^BCR::ABL1 patients was RUNX1 at 45 %. The overall survival (OS) and event-free survival (EFS) between MPAL^BCR::ABL1 and AML^BCR::ABL1 significantly differed, conferring a better prognosis for patients with MPAL^BCR::ABL1.

Our results indicate that adult patients with MPAL^BCR::ABL1 present with younger age and may have better survival outcomes than patients with AML^BCR::ABL1. In addition, our next-generation sequencing (NGS) data indicates that RUNX1 is frequently mutated in B/myeloid MPAL^BCR::ABL1 compared to AML^BCR::ABL1. Future studies are warranted to further elucidate the role of RUNX1 in this disease.