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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
Lund University, Sweden .
Skåne University Hospital, Lund, Sweden .
Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
Lund University, Sweden .
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2014 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 28, no 2, 302-310 p.Article in journal (Refereed) Published
Abstract [en]

Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. As 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 the 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 during 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 (greater than= 10 years), white blood cell counts (greater than100 x 10(9)/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 the risk group. Older age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.

Place, publisher, year, edition, pages
Nature Publishing Group, 2014. Vol. 28, no 2, 302-310 p.
Keyword [en]
pediatric acute lymphoblastic leukemia; single-nucleotide polymorphism array analyses; relapse; IKZF1; SPRED1
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-105416DOI: 10.1038/leu.2013.206ISI: 000331223900009PubMedID: 23823658OAI: diva2:706650
Available from: 2014-03-21 Created: 2014-03-21 Last updated: 2014-03-28Bibliographically approved

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ReferencesLink to record
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