Secondary acute monocytic leukemia positive for 11q23 rearrangement in Nijmegen breakage syndrome

Pediatr Blood Cancer. 2014 Aug;61(8):1469-71. doi: 10.1002/pbc.24994. Epub 2014 Mar 11.

Abstract

Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability disorder characterized by a high incidence of pediatric hematologic malignancies. Majority of patients affected are of Slavic origin and share the same founder mutation of 657del5 within the NBN gene encoding protein involved in DNA double-strand breaks (DSB) repair. We report a case of a pediatric patient with NBS, who developed t(9;11)/AF9-MLL-positive AML as a second malignancy after successful treatment of T-NHL. The coexistence of NBN and MLL mutations suggests that the profound dysfunction of NBN may promote alterations of MLL that is mediated by error-prone non-homologous end joining pathway particularly in patients treated with DNA topoisomerase II inhibitors.

Keywords: MLL; acute myeloid leukemia; gene; nijmegen breakage syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cell Cycle Proteins / genetics
  • Chromosomes, Human, Pair 11 / genetics*
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, Monocytic, Acute / etiology*
  • Leukemia, Monocytic, Acute / genetics
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Nijmegen Breakage Syndrome* / complications
  • Nijmegen Breakage Syndrome* / genetics
  • Nuclear Proteins / genetics
  • Translocation, Genetic*

Substances

  • Cell Cycle Proteins
  • KMT2A protein, human
  • NBN protein, human
  • Nuclear Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase