期刊
BLOOD
卷 114, 期 5, 页码 1038-1045出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-12-192039
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资金
- National Institutes of Health [R01CA120196, R01CA129382, CA114737, CA02111]
- ECOG's Leukemia Tissue Bank
- WOLF Foundation
- Leukemia & Lymphoma Society [1287-08, 6237-08]
- Charlotte Geyer Foundation
- Cancer Research Institute
- Swim Across America Foundation
- Golfers Against Cancer Foundation
- Leukemia Research Fund
- Medical Research Council of Great Britain
- Fondo de Investigacion Sanitaria [CD07/00033]
- Leukemia & Lymphoma Society Scholar
- Alex's Lemonade Stand Foundation
- Medical Research Council [G0500389, MC_U137686856] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10370] Funding Source: researchfish
- MRC [G0500389, MC_U137686856] Funding Source: UKRI
The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed that diagnosis and relapsed cases have common genetic alterations, but also that relapsed samples frequently lose chromosomal markers present at diagnosis, suggesting that relapsed T-ALL emerges from an ancestral clone different from the major leukemic population at diagnosis. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2 of 9 samples. Subsequent analysis showed WT1 mutations in 28 of 211 (13.2%) of pediatric and 10 of 85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frame-shift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3, and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall, these results identify the presence of WT1 mutations as a recurrent genetic alteration in T-ALL. (Blood. 2009; 114: 1038-1045)
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