An 11-month-old girl presented with pallor, bruising, lethargy, anemia (hemoglobin, 68 g/L), leukocytosis (30.2 × 109/L), and thrombocytopenia (13 × 109/L). A peripheral blood smear showed numerous large blasts with a high nucleus-to-cytoplasm ratio, open chromatin, and prominent nucleoli (panels A-B; Wright-Giemsa stain, 100× objective). Flow cytometry (panels C-D) revealed a large population with dim CD45, low side scatter, expressing CD19, CD20, variable CD10, cytoplasmic CD79a, and surface λ light chain restriction, but not CD34, CD64, CD15, and terminal deoxynucleotidyltransferase (TdT). Bone marrow examination revealed 98% blasts with similar morphology and immunophenotype. Cytogenetic analysis showed a complex karyotype with chromosome 11 aberration (panel E). Fluorescence in situ hybridization using KMT2A break-apart probes demonstrated loss of the 3′ probe in the derivative chromosome 11, indicating a likely KMT2A rearrangement (panel F). RNA sequencing confirmed a KMT2A::AF9 (MLLT3) rearrangement and a subclonal STAG2 alteration. No translocations involving MYC, BCL2, or BCL6 were detected. These findings support a diagnosis of B-lymphoblastic leukemia (B-ALL) with KMT2A rearrangement.
B-ALL with a mature B-cell phenotype and surface light chain expression and lacking traditional immaturity markers (CD34, TdT) is exceedingly rare. B-ALL with KMT2A rearrangement has been reported to present with λ light-chain restriction. This case highlights the importance of integrating clinical presentation with comprehensive cytogenetic and molecular analyses to facilitate the diagnosis of these rare B-ALL subtypes.
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