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Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome.

Ågerstam, Helena LU ; Lilljebjörn, Henrik LU orcid ; Lassen, Carin LU ; Swedin, Agneta ; Richter, Johan LU ; Vandenberghe, Peter ; Johansson, Bertil LU and Fioretos, Thoas LU (2007) In Genes, Chromosomes and Cancer 46(7). p.635-643
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
46
issue
7
pages
635 - 643
publisher
Wiley-Liss Inc.
external identifiers
  • wos:000246413700002
  • scopus:34249081692
ISSN
1045-2257
DOI
10.1002/gcc.20442
language
English
LU publication?
yes
id
bc0dc3a8-ce48-4292-af22-9b762d52e9fa (old id 166156)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17394134&dopt=Abstract
date added to LUP
2016-04-01 12:32:40
date last changed
2025-04-04 15:23:29
@article{bc0dc3a8-ce48-4292-af22-9b762d52e9fa,
  abstract     = {{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.}},
  author       = {{Ågerstam, Helena and Lilljebjörn, Henrik and Lassen, Carin and Swedin, Agneta and Richter, Johan and Vandenberghe, Peter and Johansson, Bertil and Fioretos, Thoas}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{635--643}},
  publisher    = {{Wiley-Liss Inc.}},
  series       = {{Genes, Chromosomes and Cancer}},
  title        = {{Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome.}},
  url          = {{http://dx.doi.org/10.1002/gcc.20442}},
  doi          = {{10.1002/gcc.20442}},
  volume       = {{46}},
  year         = {{2007}},
}