KMT2A (MLL1) Rearrangements in Hematolymphoid Malignancies: A Genomic Landscape Study

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.1567-1567
• Main Authors: Ghimire, Krishna, Goodman, Alexandra, Sampat, Parth, Srivastava, Nimisha, Nam, Myungwoo, Ross, Jeffrey
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-211191

Background: KMT2A (MLL1) gene is altered in a variety of hematolymphoid neoplasms and solid tumors. In acute myelocytic leukemia, the interactions between KMT2A gene fusion proteins and menin have been linked to leukemogenesis and represent new potential targets for anti-tumor therapies. Methods: 4,190 cases of AML underwent comprehensive genomic profiling using the Foundation One Heme combined hybrid capture based DNA and RNA sequencing assay. All classes of genomic alterations (GA) were evaluated. The tumor mutation burden (TMB) and microsatellite stability (MSS) status were determined from the sequencing data. Results: Of the 4,190 AML cases, there were 43.1% female and 56.9% male patients with a median age of 62 years. 520 (12.4%) of the AML cases featured a GA in the KMT2A gene 99.1% of which were large rearrangements (KMT2Ara). The KMT2Ara AML cases had a median age of 62 years and were 41.7% female and 58.3% male gender. In contrast, the KMT2A not rearranged (KMT2Anra) cases had a similar mean age and gender distribution. Of the KMT2Ara cases there were 43.1% KMT2A duplications, 52.7% fusions and 4.2% not otherwise specified rearrangements. 0.9% of the KMT2A altered AML cases were short variant mutations. There were no KMT2A (0%) amplifications or deletions. GA enriched in the KMT2Ara vs the KMT2Anra AML cases included significantly increased frequencies of GA in FLT3 (27.3% vs 19.9%; p=.0001), KRAS (16.0% vs 8.0%; P