Immunophenotypic and genetic features of pediatric non-DS AMKL versus non-AMKL AML: A single-center study in China

Pediatric non-Down syndrome acute megakaryoblastic leukemia (non-DS AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We retrospectively analyzed all non-DS AMKL cases diagnosed at our institute between January 2018 and June 2024 (n = 54), and randomly selected 59 non-AMKL AML patients as controls. Comparative analyses included immunophenotyping, karyotyping, fusion gene detection, and targeted next-generation sequencing. Recurrent fusion genes in the AMKL cohort included KMT2A rearrangements (n = 7), CBFA2T3::GLIS2 (n = 6), RBM15::MKL1 (n = 5), and NUP98 rearrangements (n = 3). No RBM15::MKL1 or CBFA2T3::GLIS2 fusions were detected in controls. After adjustment for age and FDR correction, AMKL remained associated with frequent CD36/CD71 expression and reduced HLA-DR, CD123, and normal-intensity CD38 expression (p < 0.05). Notably, 14 cases were CD33-positive, but CD13/CD117-negative, and 3 cases were negative for all three antigens; neither pattern was observed in controls. The most frequently mutated genes were MPL and JAK2 (11.9% each), whereas the corresponding frequencies in controls were 1.7% and 3.4%; the between-group differences were not statistically significant. Truncating GATA1 mutations occurred in 2 AMKL cases but not in controls. Pediatric non-DS AMKL exhibits high heterogeneity with recurrent fusion genes, unique immunophenotypic signatures, and a spectrum of somatic mutations.