Abstract and Introduction
Objectives: Classification of acute leukemia involves assigning lineage by resemblance to normal progenitor cells. This approach provides descriptive information about the blast cells that is useful for disease monitoring, provides clues to pathogenesis, and can help clinicians select effective chemotherapeutic regimens. Acute leukemias of ambiguous lineage (ALALs) are those leukemias that either fail to show evidence of myeloid, B-, or T-lymphoid lineage commitment or show evidence of commitment to more than 1 lineage. The different treatment regimens for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) make ALAL a challenge both diagnostically and therapeutically.
Methods: Current classification criteria have reduced the reported incidence of mixed-lineage leukemias by emphasizing fewer markers and categorizing some biphenotypic leukemias with recurrent cytogenetic abnormalities as other entities. Several recent studies have explored the genomic and epigenetic landscape of mixed-phenotype acute leukemia (MPAL) and have suggested a further refinement of the World Health Organization classification to emphasize the genomic heterogeneity of MPAL.
Results: Genomic and expression profile data for MPAL reveal mutations commonly seen in both AML and ALL, with T-/myeloid MPAL showing overlapping features with early T-cell precursor lymphoblastic leukemia.
Conclusions: Our review aimed to discuss the diagnostic challenges, recent genomic studies, and therapeutic strategies in this poorly understood disease.
Acute leukemias of ambiguous lineage (ALALs) include biologically diverse leukemias that fail to show commitment to either the myeloid, B-, or T-lymphoid lineages or show evidence of commitment to more than 1 lineage. Cases in the former group are referred to as acute undifferentiated leukemias (AULs), while those in the latter group are identified as mixed-phenotype acute leukemias (MPALs). These MPAL cases can contain more than 1 lineage-defining marker on a single blast population (biphenotypic leukemia) or 2 or more identifiable single-lineage leukemia populations (bilineal leukemia).
Overall, MPAL is uncommon, accounting for 2% to 3% of acute leukemia cases and 0.35 cases per 1,000,000 person-years; it also has a male predominance (~1:1.6). Among cases of MPAL, the B/myeloid subtype accounts for 59% of cases, whereas the T/myeloid, B/T, and trilineage subtypes account for 35%, 4%, and 2% of cases, respectively. The different treatment regimens for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) make ALAL a challenge both diagnostically and therapeutically.
Am J Clin Pathol. 2022;158(1):27-34. © 2022 American Society for Clinical Pathology