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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Linköping University Hospital
  • Skaraborg Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • 8p11 myeloproliferative syndrome, BCR/FGFR1, myeloproliferative syndrome, tyrosine kinase inhibitors
Original languageEnglish
Pages (from-to)442-448
Number of pages7
JournalEuropean Journal of Haematology
Volume99
Issue number5
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes