Abstract
The evolving stratified treatment approach based on molecular genetic alterations and minimal residual disease (MRD) monitoring has established a strong foundation for clinically managing Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). However, with the growing use of immune-targeted therapies and the increased sensitivity of detection technologies, discrepancies in MRD assessment have emerged in some patients with Ph(+) ALL, particularly where BCR:: ABL1-based MRD levels remain consistently elevated compared to those detected by alternative methods. Research suggests that this persistent BCR:: ABL1 positivity may not solely reflect residual lymphoblasts but may also indicate the involvement of multilineage hematopoietic cells. This distinct biological feature has been termed Ph(+) ALL with multilineage involvement. Currently, the absence of standardized diagnostic criteria and prognostic frameworks for this subtype poses significant challenges in clinical decision-making. Therefore, this article offers a comprehensive review of its molecular and pathological characteristics, potential prognostic biomarkers, patterns of disease evolution, and clinical implications, with the goal of informing more accurate diagnostic and therapeutic strategies.