B-cell acute lymphoblastic leukemia with MEF2D::BCL9 rearrangement mimicking a Burkitt lymphoma

A 39-year-old woman presented with widespread lymphadenopathy, leukocytosis (25.1 × 10⁹/L), anemia (hemoglobin, 9.6 g/dL), thrombocytopenia (23 × 10⁹/L), and elevated lactate dehydrogenase (8594 U/L). The peripheral blood smear showed 46% atypical cells with finely clumped chromatin, medium to large nucleoli, and basophilic cytoplasm with prominent cytoplasmic vacuoles, resembling Burkitt lymphoma cells (panel A: May-Grünwald-Giemsa stain, 100× objective, total magnification ×1000). The bone marrow was massively infiltrated. Flow cytometry analysis revealed an immature B-cell population positive for CD19, cCD79a, CD22, CD10, CD38, terminal deoxynucleotidyltransferase, and CD34(subset), but lacked expression of CD20 as well as surface and cytoplasmic immunoglobulin (panel B). Fluorescence in situ hybridization analyses were negative for MYC and BCR::ABL1 rearrangement, and cytogenetic analysis revealed a complex karyotype: 46,XX,der(1)(2pter->2p11::1p31->1q21::?::2q13->2qter),-2,-6,+2mar[20]. Optical genome mapping identified a chromothripsis-like pattern of chromosome 1 (Circos plots in panel C [arrow] and panel D), including a cryptic MEF2D::BCL9 rearrangement (panel D [arrow] and panel E). This rearrangement was confirmed by targeted RNA sequencing.

B-cell acute lymphoblastic leukemia (B-ALL) with MEF2D rearrangement is a newly recognized subclassification of B-ALL (International Consensus Classification and 5th edition of the World Health Organization classification). Previous reports have suggested that B-ALL with MEF2D::BCL9 fusion morphologically mimics Burkitt lymphoma. The case presented highlights the importance of cytogenetic and molecular tools for the subclassification of B-ALL, enabling identification of these recently described high-risk subtypes and optimization of the therapeutic approach.

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