Minor Myeloid Leukemic Populations in Pediatric Acute Lymphoblastic Leukemia: A Potentially Underrecognized...

In "bilineal" mixed-phenotype acute leukemia (MPAL), the proportions of lymphoid and myeloid leukemic cells may differ substantially. A myeloid component may constitute <10% of bone marrow (BM) cells and show subtle immunophenotypic abnormalities detectable by multicolor flow cytometry (MFC). The significance of minor myeloid leukemic populations in otherwise acute lymphoblastic leukemia (ALL), including their association with lineage switch, remains uncertain. We retrospectively reviewed diagnostic MFC data from 5094 children with B-cell precursor or T-cell ALL. An additional minor myeloid leukemic population (<10% of BM) was identified in 92 ALL cases (1.8%), with a median of 3.0% of BM cells (0.2-9.2%). The frequency of ALL cases harboring a minor myeloid leukemic population was comparable to that of overt "bilineal" MPAL (with both populations ≥ 10% of BM cells), diagnosed during the same period. The myeloid populations expressed CD33, CD64, CD14, lysozyme, and markers shared with the dominant lymphoblastic population (CD19/CD7, CD34, CD117). Common genetic findings were high hyperdiploidy (n = 14), KMT2A rearrangements (n = 13), and BCR::ABL1 (n = 8). Although no expansion was documented in most patients, 6 of 83 newly diagnosed patients (7.2%) developed lineage switch to acute myeloid leukemia or overt "bilineal" MPAL. Most cases were managed successfully with standard ALL-directed therapy.