Identification of a Cryptic Insertion ins(11;X)(q23;q28q12) Resulting in a KMT2A-FLNA Fusion in a 13-Month-Old Child with Acute Myelomonocytic Leukemia

• Published in: Cytogenetic and genome research Vol. 150; no. 3-4; p. 281
• Main Authors: Lentes, Jana, Thomay, Kathrin, Schneider, Dominik T, Bernbeck, Benedikt, Reinhardt, Dirk, Marschalek, Rolf, Meyer, Claus, Schlegelberger, Brigitte, Göhring, Gudrun
• Format: Journal Article
• Language: English
• Published: Switzerland 01.01.2016
• Subjects: Chromosome Aberrations; Chromosomes, Human, Pair 11; Filamins - genetics; Gene Fusion; Histone-Lysine N-Methyltransferase - genetics; Humans; Infant; Karyotyping; Leukemia, Myelomonocytic, Acute - genetics; Male; Myeloid-Lymphoid Leukemia Protein - genetics
• ISSN: 1424-859X
• DOI: 10.1159/000458165

In pediatric acute myeloid leukemia (AML), chromosomal abnormalities leading to a disruption of the lysine methyltransferase 2A (KMT2A) gene in 11q23 are the most frequent rearrangements. Here, we report on the identification of a novel cryptic insertion, ins(11;X)(q23;q28q12), resulting in a translocation of the KMT2A gene in 11q23, leading to a KMT2A-FLNA fusion in a 13-month-old boy with de novo acute myelomonocytic leukemia, who died 38 days after diagnosis. The patient presented a complex karyotype 48∼49,Y,del(X)(q12),+del(X)(q12),+8,ins(11;X)(q23; q28q12),+19. The identified fusion gene was predicted to be out-of-frame (fusion of portions of KMT2A exon 11 with FLNA exon 11). However, RT-PCR experiments demonstrated that a potentially functional transcript was generated by alternative splicing where KMT2A exon 10 was spliced in-frame to the truncated FLNA exon 11. This case report helps to better understand the rare but potentially severe impact of KMT2A- FLNA fusions in infants with AML to improve prognostic stratification of therapy and clinical management.