#00066456

A 55-year-old woman presented with a 2-week history of fatigue. A complete blood count showed a white blood cell count of 1.97 × 10⁹/L with 98% blasts; hemoglobin concentration, 58 g/L, and platelet count, 21 × 10⁹/L. Bone marrow aspiration showed 98% blasts (panel A; Wright-Giemsa stain, 100× objective); cytochemistry showed negative myeloperoxidase. Flow cytometry demonstrated that the blasts were positive for CD9, CD19, CD22, CD24, CD34, CD38, CD58 (dim), cytoCD79a, CD99, HLA-DR, and terminal deoxynucleotidyltransferase (panel B). Karyotyping revealed 47,XX,+X,t(8;14)(q11;q32),t(11;12)(q23;q23)[9]/46,XX[1] (panel C). Fluorescence in situ hybridization (FISH) confirmed KMT2A and IGH dual rearrangements (panel D, IGH break-apart FISH; panel E, KMT2A break-apart FISH). RNA sequencing identified KMT2A::TXNRD1 and IGH::CEBPD (whereas the breakpoint is located within SPIDR, not CEBPD) rearrangements, further confirmed by dual-color, dual-fusion FISH (panel F, KMT2A::TXNRD1 dual-fusion FISH; panel G, SPIDR::IGH dual-fusion FISH). As a consequence, the t(8;14)(q11;q32) aberration resulted in deregulation of CEBPD, but not SPIDR or a juxtaposition of CEBPD under the influence of the IGH enhancer (panel H). A diagnosis of B-lymphoblastic leukemia (B-ALL) with KMT2A::TXNRD1 and IGH::CEBPD rearrangements was rendered.

Although IGH and KMT2A rearrangements are both relatively common in B-ALL, the coexistence of IGH and KMT2A rearrangements in the same leukemic clone is exceedingly rare. To our knowledge, this is the first case of KMT2A::TXNRD1 and IGH::CEBPD corearranged B-ALL.

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