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Mixed phenotype acute leukemia: Lineage assignment, immunophenotypic classification and genetic insights.
Vasiliki Leventaki1, Sa A Wang1
1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Human Pathology
|June 25, 2026
Summary
Mixed phenotype acute leukemia (MPAL) is a rare blood cancer with complex genetic and immunophenotypic features. Understanding these characteristics is crucial for accurate diagnosis and subclassification of MPAL.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous hematologic malignancy.
- It is characterized by the presence of myeloid and lymphoid blasts or coexpression of myeloid and lymphoid markers.
- MPAL presents diagnostic and therapeutic challenges due to its complexity.
Purpose of the Study:
- To review the current understanding of the immunophenotypic and genetic landscape of MPAL.
- To emphasize the integration of diagnostic findings for MPAL subclassification.
- To highlight the importance of genomic profiling in characterizing MPAL subtypes.
Main Methods:
- Review of current literature on MPAL diagnosis and classification.
- Integration of morphologic, immunophenotypic, cytogenetic, and molecular findings.
- Analysis of diagnostic criteria from WHO and ICC classifications.
Main Results:
- MPAL classification relies on multiparameter flow cytometry, cytogenetics, and molecular studies.
- Specific genetic subtypes, including BCR::ABL1 and KMT2A rearrangements, are recognized.
- Recurrent genetic alterations in transcription factors, epigenetic regulators, and signaling pathways are identified.
Conclusions:
- Distinct genetic lesions correlate with specific immunophenotypic patterns in MPAL.
- These correlations offer insights into lineage plasticity and leukemogenesis.
- Accurate diagnosis and subclassification of MPAL require integrated analysis of diverse findings.
