Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations.
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 dele...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1797101667183755264 |
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| author | Buitenkamp, T Pieters, R Gallimore, N van der Veer, A Meijerink, J Beverloo, H Zimmermann, M de Haas, V Richards, S Vora, A Mitchell, C Russell, L Schwab, C Harrison, C Moorman, A van den Heuvel-Eibrink, MM den Boer, M Zwaan, C |
| author_facet | Buitenkamp, T Pieters, R Gallimore, N van der Veer, A Meijerink, J Beverloo, H Zimmermann, M de Haas, V Richards, S Vora, A Mitchell, C Russell, L Schwab, C Harrison, C Moorman, A van den Heuvel-Eibrink, MM den Boer, M Zwaan, C |
| author_sort | Buitenkamp, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:55:03Z |
| format | Journal article |
| id | oxford-uuid:ea3bd1b9-38e0-488f-ba3c-28447b9a3406 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:55:03Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:ea3bd1b9-38e0-488f-ba3c-28447b9a34062022-03-27T11:00:30ZOutcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ea3bd1b9-38e0-488f-ba3c-28447b9a3406EnglishSymplectic Elements at Oxford2012Buitenkamp, TPieters, RGallimore, Nvan der Veer, AMeijerink, JBeverloo, HZimmermann, Mde Haas, VRichards, SVora, AMitchell, CRussell, LSchwab, CHarrison, CMoorman, Avan den Heuvel-Eibrink, MMden Boer, MZwaan, CChildren 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. |
| spellingShingle | Buitenkamp, T Pieters, R Gallimore, N van der Veer, A Meijerink, J Beverloo, H Zimmermann, M de Haas, V Richards, S Vora, A Mitchell, C Russell, L Schwab, C Harrison, C Moorman, A van den Heuvel-Eibrink, MM den Boer, M Zwaan, C Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. |
| title | Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. |
| title_full | Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. |
| title_fullStr | Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. |
| title_full_unstemmed | Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. |
| title_short | Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. |
| title_sort | outcome in children with down s syndrome and acute lymphoblastic leukemia role of ikzf1 deletions and crlf2 aberrations |
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