Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations

被引：0
作者：
T D Buitenkamp
R Pieters
N E Gallimore
A van der Veer
J P P Meijerink
H B Beverloo
M Zimmermann
V de Haas
S M Richards
A J Vora
C D Mitchell
L J Russell
C Schwab
C J Harrison
A V Moorman
M M van den Heuvel-Eibrink
M L den Boer
C M Zwaan
机构：
[1] Erasmus MC–Sophia Children’s Hospital,Department of Pediatric Oncology/Hematology
[2] Erasmus MC,Department of Clinical Genetics
[3] Working Group Hematologic Genome Diagnostics,Department of Haematology
[4] The Hague,Department of Paediatric Haematology/Oncology
[5] Acute Myeloid Leukemia-Berlin-Frankfurt-Münster Study Group,undefined
[6] Pediatric Hematology/Oncology,undefined
[7] Medical School Hannover,undefined
[8] Dutch Childhood Oncology Group,undefined
[9] Clinical Trial Service Unit,undefined
[10] University of Oxford,undefined
[11] Sheffield Children's Hospital,undefined
[12] John Radcliffe Hospital,undefined
[13] Leukaemia Research Cytogenetics Group,undefined
[14] Northern Institute for Cancer Research,undefined
[15] Newcastle University,undefined
来源：
Leukemia | 2012年 / 26卷
关键词：
Down’s syndrome; ALL; prognosis;
D O I：
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学科分类号：
摘要：
Children with Down’s syndrome (DS) have an increased risk of developing acute lymphoblastic leukemia (ALL) and have a low frequency of established genetic aberrations. We aimed to determine which genetic abnormalities are involved in DS ALL. We studied the frequency and prognostic value of deletions in B-cell development genes and aberrations of janus kinase 2 (JAK2) and cytokine receptor-like factor 2 (CRLF2) using array-comparative genomic hybridization, and multiplex ligation-dependent probe amplification in a population-based cohort of 34 Dutch Childhood Oncology Group DS ALL samples. A population-based cohort of 88 DS samples from the UK trials was used to validate survival estimates for IKZF1 and CRLF2 abnormalities. In total, 50% of DS ALL patients had ⩾1 deletion in the B-cell development genes: PAX5 (12%), VPREB1 (18%) and IKZF1 (35%). JAK2 was mutated in 15% of patients, genomic CRLF2 rearrangements in 62%. Outcome was significantly worse in patients with IKZF1 deletions (6-year event-free survival (EFS) 45±16% vs 95±4%; P=0.002), which was confirmed in the validation cohort (6-year EFS 21±12% vs 58±11%; P=0.002). This IKZF1 deletion was a strong independent predictor for outcome (hazard ratio EFS 3.05; P=0.001). Neither CRLF2 nor JAK2 were predictors for worse prognosis. If confirmed in prospective series, IKZF1 deletions may be used for risk-group stratification in DS ALL.
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页码：2204 / 2211
页数：7
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