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Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011.

Olsson, Linda LU ; Castor, Anders LU ; Behrendtz, M; Biloglav, Andrea LU ; Forestier, E; Paulsson, Kajsa LU and Johansson, Bertil LU (2014) In Leukemia 28(2). p.302-310
Abstract
Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. Since this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations we performed single nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3,... (More)
Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. Since this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations we performed single nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1, and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (10 years), WBC counts (>100 × 109/l), t(9;22)(q34;q11), MLL rearrangements, near-haploidy, and deletions of ATP10A, IKZF1, SPRED1, and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of risk group. High age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.Leukemia accepted article preview online, 4 July 2013; doi:10.1038/leu.2013.206. (Less)
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author
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type
Contribution to journal
publication status
published
subject
in
Leukemia
volume
28
issue
2
pages
302 - 310
publisher
Nature Publishing Group
external identifiers
  • pmid:23823658
  • wos:000331223900009
  • scopus:84893766383
ISSN
1476-5551
DOI
10.1038/leu.2013.206
language
English
LU publication?
yes
id
f99902df-4902-40c9-adf3-afbea868db54 (old id 3956230)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23823658?dopt=Abstract
date added to LUP
2013-08-02 12:56:10
date last changed
2017-10-01 03:17:05
@article{f99902df-4902-40c9-adf3-afbea868db54,
  abstract     = {Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. Since this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations we performed single nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1, and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (10 years), WBC counts (>100 × 109/l), t(9;22)(q34;q11), MLL rearrangements, near-haploidy, and deletions of ATP10A, IKZF1, SPRED1, and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of risk group. High age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.Leukemia accepted article preview online, 4 July 2013; doi:10.1038/leu.2013.206.},
  author       = {Olsson, Linda and Castor, Anders and Behrendtz, M and Biloglav, Andrea and Forestier, E and Paulsson, Kajsa and Johansson, Bertil},
  issn         = {1476-5551},
  language     = {eng},
  number       = {2},
  pages        = {302--310},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011.},
  url          = {http://dx.doi.org/10.1038/leu.2013.206},
  volume       = {28},
  year         = {2014},
}