Table 1_Case Report: KMT2A amplification in two adult patients with B-cell acute lymphoblastic leukemia.docx

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.

定位于染色体带11q23的KMT2A基因（KMT2A），编码一种对造血基因调控至关重要的赖氨酸甲基转移酶。尽管KMT2A重排在急性髓系白血病（AML）和B细胞急性淋巴细胞白血病（B-ALL）中较为常见，但KMT2A扩增却较为罕见，仅见于约1%的AML病例，在B-ALL中发生率更低。鉴于其罕见性，阐明B-ALL中KMT2A扩增的特征对于改善诊断与治疗至关重要。本研究报道了2例成人B-ALL伴KMT2A扩增的病例。病例1为一名58岁男性，其骨髓细胞中68.5%的细胞存在KMT2A扩增（拷贝数6~18），同时伴有复杂核型及致病性TP53变异（c.524G>A，p.Arg175His）。患者接受了诱导化疗，但于2个月后因并发症去世。病例2为一名66岁女性，其外周血细胞中87.5%的细胞存在KMT2A扩增（拷贝数8~11），同时伴有CRLF2重排，该病例为成人新发Ph样B-ALL（Ph-like B-ALL）合并KMT2A扩增的首例报道。患者病情快速恶化，于4天内死亡。除本队列中的这2例病例外，本研究还回顾了9篇已发表的B-ALL伴KMT2A扩增的病例，这些病例均频繁出现TP53变异，着重阐述了这一侵袭性白血病亚型的临床与遗传学特征。这些病例凸显了KMT2A扩增阳性B-ALL的高风险性，尤其在老年患者中，此类患者预后较差，且与TP53变异或CRLF2重排密切相关。本综述强调了通过基因分型优化风险分层与治疗方案的必要性。鉴于目前已报道的病例数量有限，亟需开展进一步研究以开发针对KMT2A扩增阳性B-ALL的更优治疗策略。