Acute Myeloid Leukemia With KMT2A Amplification: A TP53-Alteration-Enriched Subgroup Associated With Chromoanagenesis and Poor Prognosis
In brief
Venetoclax regimens extend median survival to about 7 months in KMT2A-amp AML
In a review of 96 AML patients with KMT2A amplification-most of whom had TP53 alterations and complex karyotypes-intensive chemotherapy did not improve outcomes, while venetoclax-based therapy raised median overall survival from 4.6 to 7.1 months and markedly lengthened event-free survival. The subgroup remains extremely high-risk, underscoring the need for better targeted treatments.
- Journal
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Q1)
- Published
- 17 September 2026
- Study design
- Cohort / observational study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Thura Win Htut, Wei-Ying Jen, Ghayas C Issa, Sanam Loghavi, Abhishek Maiti, Alexandre Bazinet, et al.
- PMID
- 42754231
- DOI
- 10.1016/j.modpat.2026.101086
Why clinicians should know about it
- Picked for Hematology (paper of the day, 20 September 2026): KMT2A‑amp AML shows poor prognosis, venetoclax benefit
Abstract
KMT2A amplification (KMT2A-amp) is a rare but aggressive genomic abnormality in acute myeloid leukemia (AML), with limited characterization in prior studies. We retrospectively analyzed 96 patients with AML harboring KMT2A-amp, including 56 newly diagnosed (ND) and 40 relapsed/refractory (RR) cases, with a median age of 68 years. Approximately half of the cases had therapy-related or secondary AML. All cases demonstrated highly complex karyotypes, with frequent -5/del(5q), -7/del(7q), and -17/del(17p). TP53 alteration was present in 93% of patients, whereas other recurrent AML-associated mutations were uncommon, and no AML-defining gene fusions or mutations were identified. In cases evaluated by optical genome mapping, all showed chromoanagenesis involving chromosome 11q23 region. Clinical outcomes were poor, with a median overall survival of 5.5 months in ND and 2.3 months in RR patients. Intensive chemotherapy did not improve survival compared with lower-intensity therapy, whereas venetoclax-based regimens were associated with improved overall survival (7.1 vs 4.6 months; p = 0.04) and event-free survival (6.7 vs 0.17 months; p < 0.01). We conclude that KMT2A-amp AML represents an extremely high-risk subgroup occurring in the context of TP53-associated genomic instability and chromoanagenesis. Its refractoriness to conventional chemotherapy highlights the urgent need for more effective, targeted therapeutic strategies.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.