CASE REPORT article
Front. Oncol.
Sec. Hematologic Malignancies
KMT2A Amplification in Two Adult Patients with B-Cell Acute Lymphoblastic Leukemia
Provisionally accepted
Min Gao1
Yunjia Chen1
Kimo Bachiashvili2Pankit J Vachhani2Omer Jamy1
Shuko Harada3Alexander Craig Mackinnon3Nirupama Singh3Aishwarya Ravindran3Baleed Vishnu Reddy3Andrew J Carroll1Fady M Mikhail1*- 1Department of Genetics, The University of Alabama at Birmingham, Birmingham, United States
- 2Department of Medicine (Hematology/Oncology), The University of Alabama at Birmingham, Birmingham, United States
- 3Department of Pathology, The University of Alabama at Birmingham, Birmingham, United States
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The KMT2A gene, located at chromosome band 11q23, encodes a lysine methyltransferase essential for hematopoietic gene regulation. While KMT2A rearrangements are common in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL), KMT2A amplification is rare, occurring in ~1% of AML cases and even less frequently in B-ALL. Given its rarity, understanding KMT2A amplification in B-ALL is crucial for improving diagnostics and therapy. We report two adult B-ALL cases with KMT2A amplification. Patient 1, a 58-year-old male, had KMT2A amplification (6~18 copies in 68.5% of bone marrow cells), a complex karyotype, and a pathogenic TP53 variant (c.524G>A, p.Arg175His). He underwent induction chemotherapy but passed away after two months due to complications. Patient 2, a 66-year-old female, had KMT2A amplification (8~11 copies in 87.5% of peripheral blood cells) and CRLF2 rearrangement, representing the first reported case of de novo Ph-like B-ALL with KMT2A amplification in an adult. She deteriorated rapidly and died within four days. In addition to these two cases from our cohort, we review nine published cases with KMT2A amplification in B-ALL, which showed frequent TP53 alterations, emphasizing the clinical and genetic characteristics of this aggressive leukemia subtype. These cases highlight the high-risk nature of KMT2A-amplified B-ALL, particularly in older adults, where prognosis is poor and linked to TP53 variants or CRLF2 rearrangement. Our review underscores the need for genetic profiling to improve risk stratification and treatment. Given the limited documented cases, further research is essential to develop better therapeutic strategies for KMT2A-amplified B-ALL.
Keywords: B-ALL, complex karyotype, CRLF2 rearrangement, KMT2A amplification, TP53 variant
Received: 30 Jun 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Gao, Chen, Bachiashvili, Vachhani, Jamy, Harada, Mackinnon, Singh, Ravindran, Reddy, Carroll and Mikhail. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fady M Mikhail
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