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Primary cells in BCR/FGFR1-positive 8p11 myeloproliferative syndrome are sensitive to dovitinib, ponatinib, and dasatinib

Landberg, Niklas LU ; Dreimane, Arta; Rissler, Marianne LU ; Billström, Rolf and Ågerstam, Helena LU (2017) In European Journal of Haematology 99(5). p.442-448
Abstract

Objectives: Translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene are associated with the 8p11 myeloproliferative syndrome (EMS), a rare neoplasm that following a usually short chronic phase progresses into acute myeloid or lymphoid leukemia. The treatment commonly involves chemotherapy and, if possible, allogeneic stem cell transplantation which is the only therapeutic option for long-term survival. Given the aggressive course of EMS, we here evaluated tyrosine kinase inhibitors as treatment options to delay disease progression. Methods: We described a new case of EMS and used chromosome analyses, PCR, and sequencing to investigate the underlying genetic aberrations. The sensitivity to several tyrosine kinase... (More)

Objectives: Translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene are associated with the 8p11 myeloproliferative syndrome (EMS), a rare neoplasm that following a usually short chronic phase progresses into acute myeloid or lymphoid leukemia. The treatment commonly involves chemotherapy and, if possible, allogeneic stem cell transplantation which is the only therapeutic option for long-term survival. Given the aggressive course of EMS, we here evaluated tyrosine kinase inhibitors as treatment options to delay disease progression. Methods: We described a new case of EMS and used chromosome analyses, PCR, and sequencing to investigate the underlying genetic aberrations. The sensitivity to several tyrosine kinase inhibitors was tested in vitro on the EMS cell line KG1 and on primary cells from the newly diagnosed EMS patient. Results: A translocation involving chromosomes 8 and 22 was detected, and a BCR/FGFR1 fusion gene was confirmed and characterized by sequencing. KG1 cells and primary EMS cells displayed distinct sensitivity to dovitinib, ponatinib, and dasatinib as compared to normal bone marrow control cells. Conclusions: These results suggest that treatment with tyrosine kinase inhibitors may be beneficial for patients with EMS during the search for a suitable stem cell donor and for those not eligible for transplantation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
8p11 myeloproliferative syndrome, BCR/FGFR1, myeloproliferative syndrome, tyrosine kinase inhibitors
in
European Journal of Haematology
volume
99
issue
5
pages
7 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85035224997
  • wos:000413152500009
ISSN
0902-4441
DOI
10.1111/ejh.12957
language
English
LU publication?
yes
id
7c5e4559-cf4b-4e6d-956a-44f03928d190
date added to LUP
2017-12-27 17:09:03
date last changed
2018-03-29 03:00:15
@article{7c5e4559-cf4b-4e6d-956a-44f03928d190,
  abstract     = {<p>Objectives: Translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene are associated with the 8p11 myeloproliferative syndrome (EMS), a rare neoplasm that following a usually short chronic phase progresses into acute myeloid or lymphoid leukemia. The treatment commonly involves chemotherapy and, if possible, allogeneic stem cell transplantation which is the only therapeutic option for long-term survival. Given the aggressive course of EMS, we here evaluated tyrosine kinase inhibitors as treatment options to delay disease progression. Methods: We described a new case of EMS and used chromosome analyses, PCR, and sequencing to investigate the underlying genetic aberrations. The sensitivity to several tyrosine kinase inhibitors was tested in vitro on the EMS cell line KG1 and on primary cells from the newly diagnosed EMS patient. Results: A translocation involving chromosomes 8 and 22 was detected, and a BCR/FGFR1 fusion gene was confirmed and characterized by sequencing. KG1 cells and primary EMS cells displayed distinct sensitivity to dovitinib, ponatinib, and dasatinib as compared to normal bone marrow control cells. Conclusions: These results suggest that treatment with tyrosine kinase inhibitors may be beneficial for patients with EMS during the search for a suitable stem cell donor and for those not eligible for transplantation.</p>},
  author       = {Landberg, Niklas and Dreimane, Arta and Rissler, Marianne and Billström, Rolf and Ågerstam, Helena},
  issn         = {0902-4441},
  keyword      = {8p11 myeloproliferative syndrome,BCR/FGFR1,myeloproliferative syndrome,tyrosine kinase inhibitors},
  language     = {eng},
  number       = {5},
  pages        = {442--448},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Haematology},
  title        = {Primary cells in BCR/FGFR1-positive 8p11 myeloproliferative syndrome are sensitive to dovitinib, ponatinib, and dasatinib},
  url          = {http://dx.doi.org/10.1111/ejh.12957},
  volume       = {99},
  year         = {2017},
}