Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants
| Autor: | Anne R. M. von Bergh, Oskar A. Haas, Rolf Marschalek, Helmut H. Schmidt, Sabine Strehl, Ulrich Jäger, Claus Meyer, Margit König, Ivan F. Loncarevic, Björn Schneider, Steven D.P. Moore, Jochen Harbott, Marie Jarosova |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Cancer Research Adolescent Oncogene Proteins Fusion Protein domain Biology Leukemia Myelomonocytic Acute Translocation Genetic Fusion gene hemic and lymphatic diseases Genetics medicine Humans splice Child neoplasms Gene In Situ Hybridization Aged Homeodomain Proteins medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Chromosomes Human Pair 11 Alternative splicing Myeloid leukemia Infant Histone-Lysine N-Methyltransferase Middle Aged Fusion protein Neoplasm Proteins DNA-Binding Proteins Alternative Splicing Child Preschool Leukemia Monocytic Acute Female Myeloid-Lymphoid Leukemia Protein Fluorescence in situ hybridization Chromosomes Human Pair 17 |
| Zdroj: | Genes, chromosomescancer. 45(11) |
| ISSN: | 1045-2257 |
| Popis: | The majority of translocations that involve the long arms of chromosomes 11 and 17 in acute myeloid leukemia appear identical on the cytogenetic level. Nevertheless, they are diverse on the molecular level. At present, two genes are known in 11q23 and four in 17q12-25 that generate five distinct fusion genes: MLL-MLLT6/AF17, MLL-LASP1, MLL-ACACA or MLL-SEPT9/MSF, and ZBTB16/PLZF-RARA. We analyzed 14 cases with a t(11;17) by fluorescence in situ hybridization and molecular genetic techniques and determined the molecular characteristics of their fusion genes. We identified six different gene fusions that comprised seven cases with a MLL-MLLT6/AF17, three with a MLL-SEPT9/MSF, and one each with MLL-LASP1, MLL-ACACA, and ZBTB16/PLZF-RARA fusions. In the remaining case, a MLL-SEPT6/Xq24 fusion suggested a complex rearrangement. The MLL-MLLT6/AF17 transcripts were extremely heterogeneous and the detection of seven different in-frame transcript and splice variants enabled us to predict the protein domains relevant for leukemogenesis. The putative MLL-MLLT6 consensus chimeric protein consists of the AT-hook DNA-binding, the methyltransferase, and the CXXC zinc-finger domains of MLL and the highly conserved octapeptide and the leucine-zipper dimerization motifs of MLLT6. The MLL-SEPT9 transcripts showed a similar high degree of variability. These analyses prove that the diverse types of t(11;17)-associated fusion genes can be reliably identified and delineated with a proper combination of cytogenetic and molecular genetic techniques. The heterogeneity of transcripts encountered in cases with MLL-MLLT6/AF17 and MLL-SEPT9/MSF fusions clearly demonstrates that thorough attention has to be paid to the appropriate selection of primers to cover all these hitherto unrecognized fusion variants. |
| Databáze: | OpenAIRE |
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