title: Novel Cryptic Rearrangements in Adult B-Cell Precursor Acute Lymphoblastic Leukemia Involving the MLL Gene.
abstract: MLL (mixed-lineage-leukemia) gene rearrangements are typical for acute leukemia and are associated with an aggressive course of disease, with a worse outcome than comparable case, and thus require intensified treatment. Here we describe a 69-year-old female with adult B cell precursor acute lymphoblastic leukemia (BCP-ALL) with hyperleukocytosis and immunophenotype CD10- and CD19+ with cryptic MLL rearrangements. G-banding at the time of diagnosis showed a normal karyotype: 46,XX. Molecular cytogenetics using multitude multicolor banding (mMCB) revealed a complex rearrangement of the two copies of chromosome 11. However, a locus-specific probe additionally identified that the MLL gene at 11q23.3 was disrupted, and that the 5' region was inserted into the chromosomal sub-band 4q21; thus the aberration involved three chromosomes and five break events. Unfortunately, the patient died six months after the initial diagnosis from serious infections and severe complications. Overall, the present findings confirm that, by far not all MLL aberrations are seen by routine chromosome banding techniques and that fluorescence in situ hybridization (FISH) should be regarded as standard tool to access MLL rearrangements in patients with BCP-ALL.
authors.affiliation: Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany (MAKO, MR, KR, TL)
authors.forename: Moneeb A K
authors.initials: MA
authors.lastname: Othman
authors.affiliation: Cytogenetic Laboratory, Maria Sklodowska-Curie Memorial Cancer Centre and Institute, Warsaw, Poland (BG)
authors.forename: Beata
authors.initials: B
authors.lastname: Grygalewicz
authors.affiliation: Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland (BPG)
authors.forename: Barbara
authors.initials: B
authors.lastname: Pienkowska-Grela
authors.affiliation: Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany (MAKO, MR, KR, TL)|Croatian Institute of Brain Research, Zagreb, Croatia (MR)
authors.forename: Martina
authors.initials: M
authors.lastname: Rincic
authors.affiliation: Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany (MAKO, MR, KR, TL)
authors.forename: Katharina
authors.initials: K
authors.lastname: Rittscher
authors.affiliation: Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal (JBM, IMC)|CIMAGO, Centro de Investigação em Meio Ambiente, Genéticae Oncobiologia University of Coimbra, (JBM, IMC)
authors.forename: Joana B
authors.initials: JB
authors.lastname: Melo
authors.affiliation: Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal (JBM, IMC)|CIMAGO, Centro de Investigação em Meio Ambiente, Genéticae Oncobiologia University of Coimbra, (JBM, IMC)
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira
authors.affiliation: ZytoVision GmbH, Bremerhaven, Germany (BM)
authors.forename: Britta
authors.initials: B
authors.lastname: Meyer
authors.affiliation: Department of Haematology and Bone Marrow Transplantation, Holy Cross Cancer Center, Kielce, Poland (WM)
authors.forename: Watek
authors.initials: W
authors.lastname: Marzena
authors.affiliation: Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany (MAKO, MR, KR, TL)
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
mesh_terms: D000208:Acute Disease; D000368:Aged; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D017809:Fatal Outcome; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
keywords: B-cell precursor acute lymphoblastic leukemia; MLL; array-comparative genomic hybridization; cryptic rearrangements; fluorescence in situ hybridization; mixed-lineage-leukemia gene