Acute Myeloid Leukemia With KMT2A Amplification: A TP53-Alteration-Enriched Subgroup Associated With Chromoanagenesis and Poor Prognosis.

Authors

Thura Win Htut, Wei-Ying Jen, Ghayas C Issa, Sanam Loghavi, Abhishek Maiti, Alexandre Bazinet, Jayastu Senapati, Eitan Kugler, Calos Bueso-Ramos, Qing Wei, Gokce A Toruner, Musa Yilmaz, Gautam Borthakur, Nicholas J Short, Tapan M Kadia, Farhad Ravandi, Naval G Daver, Courtney D DiNardo, Guilin Tang

Published in

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. Pages 101086. Sep 17, 2026. Epub Sep 17, 2026.

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.

PMID:
42754231
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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