Acute myeloid leukemia (AML) patients with partial tandem duplications (PTDs) in the Mixed Lineage Leukemia (MLL) officially known as the Lysine (K)-specific Methyltransferase 2A (KMT2A) gene, generally have adverse outcomes. Previous mouse studies have shown that Kmt2a-ptd is insufficient to cause AML, indicating additional mutations are required for leukemogenesis. Herein, we evaluated the mutational landscape, gene expression signatures and prognosis of KMT2A-PTD adult AML in comparison to a well-characterized adult AML cohort without KMT2A-PTD. Our study demonstrates that KMT2A-PTD AML has a distinct gene expression signature and that concomitant DNMT3A and NRAS mutations were associated with adverse clinical outcome in this subset of AML. AML patients with KMT2A-PTD is characterized by an internal duplication spanning exon 3 to 9, exon 3 to 10, or exon 3 to 11 (Fig. S1A, Supplemental Digital Content 1, http://links.lww.com/HS/A25).1KMT2A-PTDs occur in 3.2 to 11% of adult de novo AML and are more frequently present in AML with normal cytogenetics and AML with trisomy of chromosome 11 as a sole cytogenetic aberration.2 The presence of a KMT2A-PTD has been shown to associate with adverse outcome in AML.
Acute myeloid leukemia (AML) patients with partial tandem duplications (PTDs) in the Mixed Lineage Leukemia (MLL) officially known as the Lysine (K)-specific Methyltransferase 2A (KMT2A) gene, generally have adverse outcomes. Previous mouse studies have shown that Kmt2a-ptd is insufficient to cause ...
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