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Inside the Biology of Acute Leukemias of Ambiguous Lineage: Diagnostic Work-Up, Genomic and Clinical Characterization

Author(s): Binsah George, Anneliese Gonzalez, Adan Rios

Mixed-phenotype acute leukemia (MPAL) is rare subtype of leukemia characterized by blasts with both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) markers. MPAL is a high-risk disease which represents only 2%–3% of acute leukemias and involves a genetically and immunophenotypically diverse group of patients with poor clinical outcomes. The limited incidence and lack of prospective data on therapeutic outcomes poses uncertainty about the best approach for patients with MPAL. The modest evidence on therapeutic decisions is based on uncontrolled studies and retrospective data suggesting higher remission rates with an ALL-like induction approach than with an AML-like regimen followed by allogeneic stem cell transplant during the complete remission.

Advances in understanding the genetic landscape of MPAL demonstrates that most cases are associated with somatic mutations in tumor suppressors, transcription factors, and epigenetic regulators. Recent studies showed that MPALs derive from multipotent primitive cells with considerable genetic diversity, which may promote treatment with targeted therapy. Prospective studies should be prioritized to provide answers about this innately heterogeneous disease.

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