TY - JOUR
T1 - Primary cells in BCR/FGFR1-positive 8p11 myeloproliferative syndrome are sensitive to dovitinib, ponatinib, and dasatinib
AU - Landberg, Niklas
AU - Dreimane, Arta
AU - Rissler, Marianne
AU - Billström, Rolf
AU - Ågerstam, Helena
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - 8p11 myeloproliferative syndrome
KW - BCR/FGFR1
KW - myeloproliferative syndrome
KW - tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85035224997&partnerID=8YFLogxK
U2 - 10.1111/ejh.12957
DO - 10.1111/ejh.12957
M3 - Article
C2 - 28881484
AN - SCOPUS:85035224997
SN - 0902-4441
VL - 99
SP - 442
EP - 448
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 5
ER -