| Autor: |
Frank J. T. Staal, Jean-Michel Cayuela, Martin A. Horstmann, Jules P.P. Meijerink, François Sigaux, Anton W. Langerak, Jessica Buijs-Gladdines, Andrew P. Stubbs, Maartje Vuerhard, Petra Klous, Brenda Verhaaf, Anna-Sophia Wiekmeijer, Johan J. de Rooi, Valerie de Haas, Clarissa Kooi, Karin Pike-Overzet, Monique Verstegen, Berna Beverloo, Irene Homminga, Wouter de Laat, Rob Pieters, Adolfo A. Ferrando, Pieter Van lierberghe, Jean Soulier |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Blood, 116(21), 1293-1293 |
| Popis: |
Abstract 3139 To identify novel oncogenic pathways in T-cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular cytogenetic analyses. Using unsupervised and supervised analyses, we identified a novel T-ALL entity that was associated with high expression of cell cycle genes and was accordingly denoted as the proliferative cluster. Patient samples in this cluster were devoid of known oncogenic rearrangements, and clustered together with TLX1-rearranged cases in unsupervised cluster analysis suggesting pathogenic mechanisms are conserved between these cases. Alike TLX1-rearranged cases, patients within this cluster were associated with cortical thymic arrest and expressed CD1 along with CD4 and CD8. Bioinformatic analyses identified NKX2-1 as strong outlier gene that was ectopically expressed in most patients samples belonging to this cluster. One patient sample had high expression of the homologous NKX2-2 gene. Molecular-cytogenetic analyses including the Chromatine Conformation Capture on Chip (4C) method revealed various rearrangement variants of the NKX2-1 locus at 14q13 in 6 patients, including inversions to the T-cell receptor alpha/delta locus (TRAD@) at 14q11, an inversion to the IgH@ locus at 14q32 and a translocation to the TRB@ locus at 7q34. A translocation of NKX2-2 to the TRAD@ locus was identified in the case that ectopically expressed NKX2-2. All these rearrangements were novel, and have not been observed before in human cancer. NKX2-1 rearrangements could be validated in an independent T-ALL cohort. Our data strongly imply that NKX2-1/NKX2-2 represent novel oncogenes for human T-ALL. Disclosures: No relevant conflicts of interest to declare. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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