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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations.


  • Josef Davidsson
  • Kajsa Paulsson
  • David Lindgren
  • Henrik Lilljebjörn
  • T Chaplin
  • E Forestier
  • M K Andersen
  • A Nordgren
  • R Rosenquist
  • Thoas Fioretos
  • B D Young
  • Bertil Johansson

Summary, in English

Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P<0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution with some changes conserved, lost or gained (7 of 11), suggesting the presence of a preleukemic clone. This ancestral clone was characterized by numerical changes only, with structural changes and RTK-RAS mutations being secondary to the high hyperdiploid pattern.Leukemia advance online publication, 18 March 2010; doi:10.1038/leu.2010.39.


  • Division of Clinical Genetics
  • Genetic and epigenetic studies of pediatric leukemia
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year










Document type

Journal article


Nature Publishing Group


  • Cancer and Oncology



Research group

  • Genetic and epigenetic studies of pediatric leukemia


  • ISSN: 1476-5551