Primary cells in <i>BCR/FGFR1</i>‐positive 8p11 myeloproliferative syndrome are sensitive to dovitinib, ponatinib, and dasatinib

Landberg, Niklas; Dreimane, Arta; Rissler, Marianne; Billström, Rolf; Ågerstam, Helena

doi:10.1111/ejh.12957

Cited by 17 publications

(11 citation statements)

References 50 publications

(105 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While dovitinib has a high specificity for FGFR1 inhibition, ponatinib has a more broad TKI effect, and dasatinib is readily clinically available. All three TKIs exhibited a growth inhibitory effect on primary EMS leukemic cells, indicating that these drugs may be therapeutically beneficial in patients who harbor a BCR-FGFR1 translocation [40]. The use of these novel RTK therapies against EMS yet again highlights the need for personalized medicine for the treatment of oncogenic gene fusion driven cancers.…”

Section: Bcr: the Philandering Partnermentioning

confidence: 99%

BCR: a promiscuous fusion partner in hematopoietic disorders

Peiris

Donoghue

2019

Oncotarget

View full text Add to dashboard Cite

Considerable advances have been made in our understanding of the molecular basis of hematopoietic cancers. The discovery of the BCR-ABL fusion protein over 50 years ago has brought about a new era of therapeutic progress and overall improvement in patient care, mainly due to the development and use of personalized medicine and tyrosine kinase inhibitors (TKIs). However, since the detection of BCR-ABL, BCR has been identified as a commonly occurring fusion partner in hematopoietic disorders. BCR has been discovered fused to additional tyrosine kinases, including: Fibroblast Growth Factor Receptor 1 (FGFR1), Platelet-derived Growth Factor Receptor Alpha (PDGFRA), Ret Proto-Oncogene (RET), and Janus Kinase 2 (JAK2). While BCR translocations are infrequent in hematopoietic malignancies, clinical evidence suggests that patients who harbor these mutations benefit from TKIs and additional personalized therapies. The improvement of further methodologies for characterization of these fusions is crucial to determine a patient’s treatment regimen, and optimal outcome. However, potential relapse and drug resistance among patients’ highlights the need for additional treatment options and further understanding of these oncogenic fusion proteins. This review explores the mechanisms behind cancer progression of these BCR oncogenic fusion proteins, comparing their similarities and differences, examining the significance of BCR as a partner gene, and discussing current treatment options for these translocation-induced hematopoietic malignancies.

show abstract

Section: Bcr: the Philandering Partnermentioning

confidence: 99%

BCR: a promiscuous fusion partner in hematopoietic disorders

Peiris

Donoghue

2019

Oncotarget

View full text Add to dashboard Cite

show abstract

“…There are a few reported patients who have been treated unsuccessfully with hydroxyurea [6], chemotherapy or TKIs [2, 5]. More potent TKIs, such as ponatinib which exhibits pan-FGFR inhibitory activity, may be of clinical benefit [10, 11]. Cardiovascular risk factors precluded the use of ponatinib in our case.…”

Section: Discussionmentioning

confidence: 94%

A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

Villafuerte-Gutierrez

Rubio

Herrera

et al. 2018

Case Reports in Hematology

View full text Add to dashboard Cite

Hematopoietic myeloproliferative neoplasms with FGFR1 rearrangement result in the 8p11 myeloproliferative syndrome that in the current Word Health Organization classification is designated as “myeloid and lymphoid neoplasm with FGFR1 abnormalities.” We report the case of a 66-year-old man who had clinical features that resembled chronic myeloid leukaemia (CML), but bone marrow cytogenetic and fluorescent in situ hybridization (FISH) studies showed t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. He was initially managed with hydroxyurea, and given the aggressive nature of this disease, four months later, the patient underwent an allogeneic hematopoietic stem-cell transplantation (HSCT) from an HLA-haploidentical relative. Currently, HSCT may be the only therapeutic option for long-term survival at least until more efficacious tyrosine kinase inhibitors (TKIs) become available.

show abstract

“…With respect to the effect of Dasatinib on FGFR1 (also reported in our analysis, Figure 1B), the sensitivity to Dasatinib as a tyrosine kinase inhibitor has been tested in vitro on an 8p11 myeloproliferative syndrome (using cell lines and primary cells of this rare tumor). Distinct sensitivity to Dasatinib was proven on these cells as compared with normal bone marrow control cells [39]. These cells presented translocations involving the fibroblast growth factor receptor 1 (FGFR1), as well as a BCR/FGFR1 fusion gene (confirmed and characterized by sequencing), indicating that Dasatinib somehow affects the cells where FGFR1 has specific alterations.…”

Section: Collection and Integration Of Cancer Gene Expression And Drumentioning

confidence: 88%

Mining Drug-Target Associations in Cancer: Analysis of Gene Expression and Drug Activity Correlations

et al. 2020

View full text Add to dashboard Cite

Cancer is a complex disease affecting millions of people worldwide, with over a hundred clinically approved drugs available. In order to improve therapy, treatment, and response, it is essential to draw better maps of the targets of cancer drugs and possible side interactors. This study presents a large-scale screening method to find associations of cancer drugs with human genes. The analysis is focused on the current collection of Food and Drug Administration (FDA)-approved drugs (which includes about one hundred chemicals). The approach integrates global gene-expression transcriptomic profiles with drug-activity profiles of a set of 60 human cell lines obtained for a collection of chemical compounds (small bioactive molecules). Using a standardized expression for each gene versus standardized activity for each drug, Pearson and Spearman correlations were calculated for all possible pairwise gene-drug combinations. These correlations were used to build a global bipartite network that includes 1007 gene-drug significant associations. The data are integrated into an open web-tool called GEDA (Gene Expression and Drug Activity) which includes a relational view of cancer drugs and genes, disclosing the putative indirect interactions found for FDA-approved drugs as well as the known targets of these drugs. The results also provide insight into the complex action of pharmaceuticals, presenting an alternative view to address predicted pleiotropic effects of the drugs.

show abstract

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

Abstract: 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.

Cited by 17 publications

References 50 publications

BCR: a promiscuous fusion partner in hematopoietic disorders

BCR: a promiscuous fusion partner in hematopoietic disorders

A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

Mining Drug-Target Associations in Cancer: Analysis of Gene Expression and Drug Activity Correlations

Contact Info

Product

Resources

About