First case of B ALL with KMT2A-MAML2 rearrangement: a case report

BMC Cancer. 2017 May 23;17(1):363. doi: 10.1186/s12885-017-3368-4.

Abstract

Background: A large number of chromosomal translocations of the human KMT2A gene, better known as the MLL gene, have so far been characterized. Genetic rearrangements involving KMT2A gene are frequently involved in lymphoid, myeloid and mixed lineage leukemia. One of its rare fusion partners, the mastermind like 2 (MAML2) gene has been reported in four cases of myeloid neoplasms after chemotherapy so far: two acute myeloid leukemias (AML) and two myelodysplasic syndrome (MDS), and two cases of secondary T-cell acute lymphoblastic leukemia (T-ALL).

Case presentation: Here we report the case of a KMT2A - MAML2 fusion discovered by Next-Generation Sequencing (NGS) analysis in front of an inv11 (q21q23) present in a 47-year-old female previously treated for a sarcoma in 2014, who had a B acute lymphoid leukemia (B ALL).

Conclusion: It is, to our knowledge, the first case of B acute lymphoblastic leukemia with this fusion gene. At the molecular level, two rearrangements were detected using RNA sequencing juxtaposing exon 7 to exon 2 and exon 9 to intron 1-2 of the KMT2A and MAML2 genes respectively, and one rearrangement using Sanger sequencing juxtaposing exon 8 and exon 2.

Keywords: KMT2A rearrangement; MAML2 gene; Next-Generation Sequencing; Secondary ALL.

Publication types

  • Case Reports

MeSH terms

  • B-Lymphocytes / pathology
  • DNA-Binding Proteins / genetics*
  • Exons / genetics
  • Female
  • Gene Rearrangement
  • High-Throughput Nucleotide Sequencing
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Leukemia, Biphenotypic, Acute / genetics*
  • Leukemia, Biphenotypic, Acute / pathology
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Nuclear Proteins / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Trans-Activators
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • MAML2 protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase