title: An unusual case of high hyperdiploid childhood ALL with cryptic BCR/ABL1 rearrangement.
abstract: BACKGROUND
  Both high hyperdiploidy (HeH) and the translocation t(9;22)(q34;q11) are recurrent abnormalities in childhood B-cell acute lymphoblastic leukemia (ALL) and both are used in current classification to define different genetic and prognostic subtypes of the disease. The coexistence of these two primary genetic aberrations within the same clone is very rare in children with ALL. Here we report a new case of a 17-year-old girl with newly diagnosed ALL and uncommon cytogenetic and clinical finding combining high hyperdiploidy and a cryptic BCR/ABL1 fusion and an inherited Charcot-Marie-Tooth neuropathy detected during the induction treatment.
  
  
  RESULTS
  High hyperdiploid karyotype 51,XX,+X,+4,+14,+17,+21 without apparent structural aberrations was detected by conventional cytogenetic analysis and multicolor FISH. A cryptic BCR/ABL1 fusion, which was caused by the insertion of part of the ABL1 gene into the 22q11 region, was proved in HeH clone by FISH, RT-PCR and CGH-SNP array. In addition, an abnormal FISH pattern previously described as the deletion of the 3'BCR region in some BCR/ABL1 positive cases was not proved in our patient.
  
  
  CONCLUSIONS
  A novel case of extremely rare childhood ALL, characterized by HeH and a cryptic BCR/ABL1 fusion, is presented and to the best of our knowledge described for the first time. The insertion of ABL1 into the BCR region in malignant cells is supposed. Clearly, further studies are needed to determine the genetic consequences and prognostic implications of these unusual cases.
authors.affiliation: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Libuse
authors.initials: L
authors.lastname: Lizcova
authors.affiliation: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanova
authors.affiliation: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Halka
authors.initials: H
authors.lastname: Lhotska
authors.affiliation: CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Zuna
authors.affiliation: CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Hovorkova
authors.affiliation: CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ester
authors.initials: E
authors.lastname: Mejstrikova
authors.affiliation: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Malinova
authors.affiliation: Department of Medical Genetics, Faculty Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Rabasova
authors.affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Raska
authors.affiliation: Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sramkova
authors.affiliation: Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.affiliation: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalova
keywords: BCR/ABL1 fusion; CGH–SNP array; FISH; High-hyperdiploid childhood ALL; Ph-negative childhood ALL