title: 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.
abstract: 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.
authors.affiliation: Department of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Lentes
authors.forename: Kathrin
authors.initials: K
authors.lastname: Thomay
authors.forename: Dominik T
authors.initials: DT
authors.lastname: Schneider
authors.forename: Benedikt
authors.initials: B
authors.lastname: Bernbeck
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
mesh_terms: D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D064448:Filamins / Q000235:genetics*; D050939:Gene Fusion; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007621:Karyotyping; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*
chemical_list: C578663:FLNA protein, human; D064448:Filamins; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase