A new variant of KMT2A(MLL)-FLNA fusion transcript in acute myeloid leukemia with ins(X;11)(q28;q23q23)

Cancer Genet. 2015 Apr;208(4):148-51. doi: 10.1016/j.cancergen.2015.03.001. Epub 2015 Mar 7.

Abstract

The KMT2A gene (previously known as MLL) located at 11q23 is often involved in recurrent chromosomal translocations that lead to the development of acute leukemia, particularly in infants. Acute leukemias with KMT2A rearrangements have different prognoses, which depend on the partner gene involved in the translocation. The detection of all possible types of KMT2A gene rearrangements is of key importance for the identification of biological subgroups, which may differ in clinical outcome. In this report, we describe a case study of a 7-month-old boy who presented with AML-M4; however, no obvious 11q23 rearrangement was detected in the analyzed karyotype. Fluorescence in situ hybridization evaluation showed a nonstandard signal distribution in blast cells, corresponding to the presence of two KMT2A copies and one additional copy of 5'-KMT2A inserted into the long arm of the X chromosome (ins(X;11)(q28;q23q23)). Subsequent molecular analysis showed a novel variant form of the previously described KMT2A-FLNA fusion gene, in which the KMT2A intron 9 is fused to the FLNA exon 16.

Keywords: FISH; LDI-PCR; MLL/KMT2A; acute myeloblastic leukemia; cytogenetics.

Publication types

  • Case Reports

MeSH terms

  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, X*
  • Filamins / genetics*
  • Genetic Variation
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Infant
  • Karyotyping
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Mutagenesis, Insertional
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Recombinant Fusion Proteins / genetics

Substances

  • FLNA protein, human
  • Filamins
  • KMT2A protein, human
  • Recombinant Fusion Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase