Detection of KMT2A Partial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes

partial tandem duplication (PTD) involves intragenic duplications and has been associated with poorer prognosis. In this study, we evaluated PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal ( = 21) or non-complex ( = 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, with ITD and prevalent in AML and and common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detecting PTD. Neoplasms with PTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients with PTD are generally refractory to conventional therapy, except for de novo AML.