An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL)

Area of Science:

• Hematology
• Oncology
• Immunophenotyping

Background:

• Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia, accounting for 2-5% of cases.
• MPAL is characterized by blast cells expressing multilineage immunophenotypic markers, indicating a shared B/T/myeloid phenotype.
• Historical diagnostic challenges have led to poorly characterized genetics and clinical features of MPAL.

Purpose of the Study:

• To review the updated classification of MPAL based on World Health Organization guidelines.
• To elucidate the biology, clinical features, and genetic landscape of MPAL.
• To outline current and emerging treatment strategies for MPAL.

Main Methods:

• Review of World Health Organization classifications (2008, 2016) for defining myeloid, B, and T lymphoid lineages.
• Analysis of immunophenotypic markers such as myeloperoxidase, CD19, and cytoplasmic CD3.
• Synthesis of existing literature on MPAL genetics, clinical presentation, and treatment outcomes.

Main Results:

• MPAL diagnosis relies on specific immunophenotypic markers for myeloid (myeloperoxidase), B-lymphoid (CD19), and T-lymphoid (cytoplasmic CD3) lineages.
• MPAL generally presents with a worse prognosis compared to acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL).
• Limited prospective trial data exists, with treatment often based on ALL-like regimens followed by consolidation chemotherapy or hematopoietic stem cell transplant (HSCT).

Conclusions:

• Updated classifications provide clearer diagnostic criteria for MPAL.
• MPAL represents a distinct entity with unique biological and clinical characteristics.
• Standardized treatment protocols are needed, with current approaches involving intensive chemotherapy and HSCT.