Acute myeloid/T-lymphoblastic leukemia (AMTL): A distinct category of acute leukemias with common pathogenesis in need of improved therapy

Advances in the immunophenotypic and cytogenetic classification of acute leukemias have led to improved clinical outcomes for a substantial fraction of patients. However, resistance to chemotherapy remains a major barrier to cure for patients with specific subsets of acute myeloid and lymphoblastic leukemias. Here, we propose that a molecularly distinct subtype of acute leukemia with shared myeloid and T-cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukemia (AMTL), and has been divided between 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-cell lymphoid lineages. This new diagnostic group is supported by the i) shared hematopoietic ontogeny in which myeloid differentiation potential is specifically retained during early T-cell lymphoid development, ii) recognition of cases of AML with hallmarks of T-cell development such as clonal rearrangements of the T-cell receptor genes, and iii) identification of common gene mutations in subsets of AML and T-ALL cases. This proposed diagnostic entity overlaps with early T-cell precursor (ETP) T-ALL and T-cell/myeloid mixed phenotype acute leukemias (MPAL), and also includes a subset of leukemias currently classified as AML with hallmarks of T-lymphoblastic development. AMTLs express variable levels of both T-cell and myeloid-specific markers, such as CD3 and myeloperoxidase, and additionally have shared gene mutations including WT1, PHF6, RUNX1 and BCL11B . The proposed classification of AMTL as a distinct entity should enable prospective diagnosis and development of improved therapies for patients whose treatment is inadequate with current approaches.