Case Report: KMT2A amplification in two adult patients with B-cell acute lymphoblastic leukemia

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.