Thoas Fioretos
Research team manager
Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome.
Author
Summary, in English
The 8p11 myeloproliferative syndrome (EMS) is a chronic myeloproliferative disorder molecularly characterized by fusion of various 5' partner genes to the 3' part of the fibroblast growth factor receptor 1 (FGFR1) gene at 8p, resulting in constitutive activation of the tyrosine kinase activity contained within FGFR1. EMS is associated with a high risk of transformation to acute myeloid leukemia (AML), but the mechanisms underlying the disease progression are unknown. In the present study, we have investigated a case of EMS harboring a t(8;22)(p11; q11)/BCR-FGFR1 rearrangement as well as a t(9;21)(q34;q22) at the time of AML transformation. FISH and RT-PCR analyses revealed that the t(9;21) leads to a fusion gene consisting of the 5' part of RUNX1 (exons 1-4) fused to repetitive sequences of a gene with unknown function on chromosome 9, adding 70 amino acids to RUNX1 exon 4. The t(9;21) hence results in a truncation of RUNX1. No point mutations were found in the other RUNX1 allele. The most likely functional outcome of the rearrangement was haploinsufficiency of RUNX1, which thus may be one mechanism by which EMS transforms to AML. (c) 2007 Wiley-Liss, Inc.
Department/s
- Division of Clinical Genetics
- Division of Molecular Medicine and Gene Therapy
Publishing year
2007
Language
English
Pages
635-643
Publication/Series
Genes, Chromosomes and Cancer
Volume
46
Issue
7
Links
Document type
Journal article
Publisher
John Wiley & Sons Inc.
Topic
- Medical Genetics
Status
Published
ISBN/ISSN/Other
- ISSN: 1045-2257