AUTHOR=Wang Liang , Qiu Fangzhou , Shen Yongming , Chen Sen , Si Ping 

TITLE=Co-existence of KMT2A::SEPTIN6 fusion and DIS3 variant in a pediatric case with acute myeloid leukemia: a case report and literature review

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1308786

DOI=10.3389/fonc.2023.1308786

ISSN=2234-943X

ABSTRACT=<p>The lysine(K)-specific methyltransferase 2A gene (<italic>KMT2A</italic>), previously known as mixed lineage leukemia (<italic>MLL</italic>), frequently rearranged in acute leukemia, belongs to one of the most promiscuous genes and has been found fused to more than 80 different partners. <italic>KMT2A</italic>::<italic>SEPTIN6</italic> fusion is a relatively uncommon rearrangement observed in pediatric acute myeloid leukemia (AML) patients, some of which may harbor other mutations. We herein report a case of AML-M4-infant with <italic>KMT2A</italic>::<italic>SEPTIN6</italic> fusion and <italic>DIS3</italic> variant. The 8-month-old girl presented with leukocytosis, anemia and thrombocytopenia. A bone marrow smear disclosed that 64% of the total nucleated cells were blasts. Karyotype analysis showed 46,X,t(X;11)(q24;q23)[10]/46,XX[10]. Fluorescence <italic>in situ</italic> hybridization analysis suggested a possible break in the <italic>KMT2A</italic> gene. After whole transcriptome sequencing, Exon 9 of <italic>KMT2A</italic> was fused in-frame with Exon 2 of <italic>SEPTIN6</italic>. This is a typical type of chromosomal rearrangement leading to the <italic>KMT2A</italic>::<italic>SEPTIN6</italic> fusion. Meanwhile, <italic>DIS3</italic> variant [c.2065C&gt;T, p.R689X, variant allele frequency (VAF): 39.8%] was identified. <italic>KMT2A</italic>::<italic>SEPTIN6</italic> fusion has been associated with the pathogenesis of AML, whereas <italic>DIS3</italic> variants are relatively rare genetic events in pediatric AML. Regrettably, the relatives disagreed with the combination chemotherapy, and the patient eventually died of progressive disease. In conclusion, our findings provide a foundation for a better understanding of the genotypic profile of <italic>KMT2A</italic>::<italic>SEPTIN6</italic> associated AML, and the co-existence of <italic>KMT2A</italic>::<italic>SEPTIN6</italic> and <italic>DIS3</italic> variant might contribute to the disease progression and transformation of AML.</p>