title: Secondary acute monocytic leukemia positive for 11q23 rearrangement in Nijmegen breakage syndrome.
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.
authors.affiliation: Department of Pediatrics, Hematology, Oncology & Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Pastorczak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.forename: Joanna
authors.initials: J
authors.lastname: Trelinska
authors.forename: Julio
authors.initials: J
authors.lastname: Finalet Ferreiro
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Mycko
authors.forename: Anna
authors.initials: A
authors.lastname: Polucha
authors.forename: Lukasz
authors.initials: L
authors.lastname: Sedek
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
mesh_terms: D000293:Adolescent; D018797:Cell Cycle Proteins / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000209:etiology* / Q000235:genetics; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D049932:Nijmegen Breakage Syndrome / Q000150:complications / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D018797:Cell Cycle Proteins; C497422:KMT2A protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
keywords: MLL; acute myeloid leukemia; gene; nijmegen breakage syndrome