Genetic Landscape of Acute Leukemia of Ambiguous Lineage: A Single Cancer Center Experience

Acute leukemias of ambiguous lineage (ALALs) are rare acute leukemias with poor prognosis, encompassing acute undifferentiated leukemia and mixed-phenotype acute leukemia. The fifth edition of the World Health Organization classification of hematolymphoid tumors recommends excluding ALAL cases with myelodysplasia-associated mutations and/or cytogenetic abnormalities from classification as acute undifferentiated leukemia or mixed-phenotype acute leukemia, instead categorizing them as acute myeloid leukemia with myelodysplasia (AML-MR; hereafter referred to as AML-MR/ALAL), a distinct entity with limited genetic and clinical characterization to date. In this study, the genetic and clinical characteristics of AML-MR/ALAL were investigated in comparison with those of ALAL and AML-MR. RUNX1 (7/11; 63.6%), WT1 (3/11; 27.3%), DNMT3A (2/11; 18.2%), TET2 (2/11; 18.2%), BCORL1 (2/11; 18.2%), and TP53 (2/11; 18.2%) were identified as the most frequently mutated genes in AML-MR/ALAL. Moreover, AML-MR/ALAL shared genetic features with AML-MR and was distinct from ALAL. Although no significant difference in overall survival was observed between AML-MR/ALAL and ALAL, patients with AML-MR/ALAL showed a trend toward worse prognosis. In summary, these findings suggest that AML-MR/ALAL may be more appropriately classified as AML-MR; however, validation in larger cohorts is required.