8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes

Abstract

8p11 myeloproliferative syndrome (EMS) is a clinical-pathologic entity characterized by rearrangements involving the FGFR1 gene, which encodes a receptor tyrosine kinase. These rearrangements invariably lead to aberrant fusion proteins in which the kinase activity is constitutively turned on, with resulting oncogenic properties. In this article, we describe a new translocation in EMS, t(7;8)(q34;p11), in which the FGFR1 gene is fused to a previously unidentified partner, the TIF1 gene. We show that both the TIF1-FGFR1 and FGFR1-TIF1 fusion proteins have the potential to be translated as a result of the translocation. Thus, our data extend the involvement of FGFR1 in EMS and lend support to the concept that there is a precise correlation between genotype and phenotype in this disease.

Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice

“…Clinical presentations of 5 leukemia patients (cases 1-5) with 1p36 rearrangements are shown in Supplemental Table 1. FISH mapping of translocation breakpoints as well as 5′-RACE and RT-PCR to confirm the presence of fusion genes were performed as described previously (45). Details of the bacterial artificial chromosome clones and positions of primers used are shown in Figure 1, and primer sequences are shown in Supplemental Table 2.…”

Myeloproliferative disorders: the centrosome connection

“…BCR-FGFR1 is not directly targeted to the centrosome even if signalling could relay at this organelle. 22 The recently discovered TIF1-FGFR1 fusion 27 is not suggestive of a centrosome localisation.…”

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

“…[37][38][39][40] Additional fusion partners for FGFR1, including BCR, have since been described (Table 5). [41][42][43][44][45][46][47] The FGFR1 rearrangement can be found in both myeloid and lymphoid cells, suggesting an origin in a multipotent hematopoietic progenitor, and thus the basis for the disease's alternate designation of 'stem cell leukemia/ lymphoma syndrome.' EMS manifests an aggressive course and therefore early allogeneic transplantation is often recommended.…”