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Comprehensive genetic characterization of pediatric T-cell acute lymphoblastic leukemia

  • Kristina Karrman
  • Anders Castor
  • Mikael Behrendtz
  • Erik Forestier
  • Linda Olsson
  • Mats Ehinger
  • Andrea Biloglav
  • Thoas Fioretos
  • Kajsa Paulsson
  • Bertil Johansson
Publishing year: 2014-12-06
Language: English
Pages: 1084-1084
Publication/Series: Blood
Volume: 124
Issue: 21
Document type: Conference paper: abstract
Publisher: American Society of Hematology

Abstract english

A comprehensive genetic characterization comprising conventional chromosome banding, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) array analyses as well as large-scale sequencing of 75 genes were performed on a consecutive series of 47 pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. An abnormal karyotype was identified in 46% of the cases. Recurrent cytogenetic aberrations comprised T-cell receptor (TCR) translocations and deletions of 6q and 9p. FISH analyses of TCR rearrangements were positive in 26% of the investigated cases. The vast majority (37/39; 95%) of cases analyzed by SNP arrays displayed aberrations, with a median of 3 changes (range 0-11) per case. The genes recurrently deleted were CDKN2A, CDKN2B, LEF1, PTEN, RBI, and STIL. One case displayed chromothripsis involving 6q. No case had a whole chromosome uniparental isodisomy (wUPID); in fact, only one T-ALL of 123 informative cases in the literature has had a wUPID. However, segmental UPIDs (sUPIDs) were seen in 44% of the present cases, with most being sUPID9p. CDKN2A was homozygously deleted in all cases with sUPID9p, with a heterozygous deletion occurring prior to the sUPID9p in all instances. There was no evidence for chromosomal instability when comparing diagnostic and relapse samples. Among the genes sequenced, 14 were mutated in 28 cases. The genes targeted are involved in signaling transduction, epigenetic regulation, and transcription. In some cases, NOTCH1 mutations were seen in minor subclones and lost at relapse, showing that such mutations also can be secondary events. These findings support a multistep leukemogenic process.


  • Medical Genetics
  • T lymphocyte receptor
  • T lymphocyte
  • acute lymphoblastic leukemia
  • American
  • society
  • hematology
  • gene
  • mutation
  • relapse
  • chromosome
  • chromosome aberration
  • human
  • patient
  • single nucleotide polymorphism
  • fluorescence in situ hybridization
  • diagnosis
  • chromosomal instability
  • uniparental disomy
  • chromosome banding pattern


56th Annual Meeting of the American Society of Hematology
  • Genetic and epigenetic studies of pediatric leukemia
  • ISSN: 1528-0020
Thoas Fioretos
E-mail: thoas.fioretos [at]

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67