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

The <i>KMT2A</i> gene, located at chromosome band 11q23, encodes a lysine methyltransferase essential for hematopoietic gene regulation. While <i>KMT2A</i> rearrangements are common in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL), <i>KMT2A</i> amplification is rare, occurring in ~1% of AML cases and even less frequently in B-ALL. Given its rarity, understanding <i>KMT2A</i> amplification in B-ALL is crucial for improving diagnostics and therapy. We report two adult B-ALL cases with <i>KMT2A</i> amplification. Patient 1, a 58-year-old male, had <i>KMT2A</i> amplification (6~18 copies in 68.5% of bone marrow cells), a complex karyotype, and a pathogenic <i>TP53</i> 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 <i>KMT2A</i> amplification (8~11 copies in 87.5% of peripheral blood cells) and <i>CRLF2</i> rearrangement, representing the first reported case of <i>de novo</i> Ph-like B-ALL with <i>KMT2A</i> 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 <i>KMT2A</i> amplification in B-ALL, which showed frequent <i>TP53</i> alterations, emphasizing the clinical and genetic characteristics of this aggressive leukemia subtype. These cases highlight the high-risk nature of <i>KMT2A</i>-amplified B-ALL, particularly in older adults, where prognosis is poor and linked to <i>TP53</i> variants or <i>CRLF2</i> 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 <i>KMT2A</i>-amplified B-ALL.