Background/Aim: Fusion of histone-lysine Nmethyltransferase 2A gene (KMT2A) with the Rho guanine nucleotide exchange factor 12 gene (ARHGEF12), both located in 11q23, was reported in some leukemic patients. We report a KMT2A-ARHGEF12 fusion occurring during treatment of a pediatric acute myeloid leukemia (AML) with topoisomerase II inhibitors leading to a secondary acute lymphoblastic leukemia (ALL). Materials and Methods: Multiple genetic analyses were performed on bone marrow cells of a girl initially diagnosed with AML. Results: At the time of diagnosis with AML, the t(9;11)(p21;q23)/KMT2A-MLLT3 genetic abnormality was found. After chemotherapy resulting in AML clinical remission, a 2 Mb deletion in 11q23 was found generating a KMT2AARHGEF12 fusion gene. When the patient later developed B lineage ALL, a t(14;19)(q32;q13), loss of one chromosome 9, and KMT2A-ARHGEF12 were detected. Conclusion: The patient sequentially developed AML and ALL with three leukemia-specific genomic abnormalities in her bone marrow cells, two of which were KMT2A-rearrangements.
Panagopoulos, I., Andersen, K., Eilert-Olsen, M., Zeller, B., Munthe-Kaas, M. C., Buechner, J., … Heim, S. (2021). Therapy-induced deletion in 11q23 leading to fusion of KMT2A with ARHGEF12 and development of B lineage acute lymphoplastic leukemia in a child treated for acute myeloid leukemia caused by t(9;11)(p21;q23)/ KMT2A-MLLT3. Cancer Genomics and Proteomics, 18(1), 67–81. https://doi.org/10.21873/CGP.20242