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

Davidsson, Josef LU ; Paulsson, Kajsa LU ; Lindgren, David LU ; Lilljebjörn, Henrik LU ; Chaplin, T; Forestier, E; Andersen, M K; Nordgren, A; Rosenquist, R and Fioretos, Thoas LU , et al. (2010) In Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 24. p.924-931
Abstract
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... (More)
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. (Less)
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Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
volume
24
pages
924 - 931
publisher
Nature Publishing Group
external identifiers
  • WOS:000277591500003
  • PMID:20237506
  • Scopus:77952485949
ISSN
1476-5551
DOI
10.1038/leu.2010.39
language
English
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yes
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98f5860d-fc21-41aa-a876-dd0e68396e61 (old id 1581936)
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http://www.ncbi.nlm.nih.gov/pubmed/20237506?dopt=Abstract
date added to LUP
2010-04-08 14:11:26
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2016-10-30 04:34:53
@misc{98f5860d-fc21-41aa-a876-dd0e68396e61,
  abstract     = {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&lt;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.},
  author       = {Davidsson, Josef and Paulsson, Kajsa and Lindgren, David and Lilljebjörn, Henrik and Chaplin, T and Forestier, E and Andersen, M K and Nordgren, A and Rosenquist, R and Fioretos, Thoas and Young, B D and Johansson, Bertil},
  issn         = {1476-5551},
  language     = {eng},
  pages        = {924--931},
  publisher    = {ARRAY(0x7a92828)},
  series       = {Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K},
  title        = {Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations.},
  url          = {http://dx.doi.org/10.1038/leu.2010.39},
  volume       = {24},
  year         = {2010},
}