Acute myeloid leukemia with BCL6 and KMT2A dual rearrangements

A 2-year-old boy was diagnosed with acute myeloid leukemia (AML) with t(10;11)(p12.31;q23.3)/KMT2A::MLLT10 rearrangement. Despite 5 lines of treatment, including a menin inhibitor and CD33-chimeric antigen receptor T-cell therapy, his disease progressed, promoting transfer to our hospital 8 months later. Upon admission, a complete blood count showed a white blood cell (leukocyte) count of 36.8 × 10⁹/L with 85% blasts (panel A; Giemsa stain, original magnification ×1000). Bone marrow analysis confirmed AML with 93% blasts (panel B; Giemsa stain, original magnification ×500). Flow cytometry showed 88% blasts positive for CD4, CD13 (partial), CD15 (partial), CD33, CD34, CD38 (decreased), CD56, CD64, CD123 (increased), CD133, HLA-DR, and MPO while negative for CD2, cytoCD3, CD5, CD7, CD14, CD19, CD36, CD117, and terminal deoxynucleotidyltransferase. Karyotyping revealed 47,XY,add(3)(q27),+mar[20]. Optical genome mapping identified t(10;11)(p12.31;q23.3)/KMT2A::MLLT10 and fus(3;3)(p24.3;q27.3)/SATB1::BCL6. Fluorescence in situ hybridization confirmed BCL6 rearrangement in 86.5% of cells (panel C). The blasts were positive for CD34 and BCL6 by immunohistochemistry (panels D-E; original magnification ×500). Immunostains for CD20, CD79a, and PAX5 revealed an absence of B cells (panel F; original magnification ×500). Next-generation sequencing revealed KRAS p.G13dup (variant allele frequency [VAF]: 49%) and ASXL1 p.G646fs∗11 (VAF: 5%). The patient received cytarabine, cladribine, and palbociclib but died 1.5 months later.

BCL6 rearrangement is commonly observed in diffuse large B-cell lymphoma and follicular lymphoma. Its detection in AML is unusual and has not been previously reported. Nonetheless, the role of BCL6 expression in AML, along with acute lymphoblastic leukemia and some solid tumors, is well studied and has been associated with chemoresistance, potentially explaining our patient’s refractory disease.

For additional images, visit the ASH Image Bank, a reference and teaching tool that is continually updated with new atlas and case study images. For more information, visit https://imagebank.hematology.org.