Mixed-phenotype acute leukemia, T/megakaryoblastic: does it really exist?

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Mixed-phenotype acute leukemias (MPAL) constitute less than 4% of acute leukemia cases and are classified as rare subtypes by the WHO.
• Diagnosis and treatment of MPAL are particularly challenging in low-middle income countries.
• While B/myeloid and T/myeloid MPAL are relatively common, combinations involving megakaryoblastic or erythroid lineages with other cell types are exceptionally rare and often not addressed in current classifications.

Purpose of the Study:

• To report the clinical presentation, diagnostic profile, and disease course of MPAL cases with a biphenotypic pattern consistent with T/megakaryoblastic lineage.
• To highlight the limitations of existing WHO classifications in addressing rare MPAL subtypes.
• To advocate for the inclusion of T/megakaryoblastic MPAL as a distinct entity in the WHO classification.

Main Methods:

• Phenotyping was performed using 8-color flow cytometry with an extensive marker panel.
• Interphase fluorescence in situ hybridization (FISH) was used to detect specific gene rearrangements (BCR::ABL1, RUNX1::RUNX1T1, ETV6::RUNX1, MLL, CBFB).
• Conventional GTG-banding karyotyping was conducted and analyzed using an automated cell imaging system.

Main Results:

• The study presents the first documented cases of T/megakaryoblastic MPAL from Pakistan.
• These cases met the criteria for both T-lineage assignment and acute megakaryoblastic leukemia.
• The findings underscore the diagnostic challenges and limitations of current classifications for rare MPAL subtypes.

Conclusions:

• T/megakaryoblastic MPAL represents a distinct and previously undefined entity.
• Reporting such rare cases is crucial for accumulating data on clinical presentation, diagnostics, and disease course.
• The WHO classification needs revision to include T/megakaryoblastic MPAL as a separate category to improve diagnosis and management.