Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several recurrent translocations that involve chromosome band 8p11 have been described in myeloid malignancies. These translocations target two distinct genes: (1) FGFR1, a receptor tyrosine kinase for fibroblast growth factors, and (2) MOZ, a putative histone acetyltransferase whose precise function remains to be defined. Disruption of FGFR1 is associated with a disease entity known as the 8p11 myeloproliferative syndrome (EMS)/stem cell leukemia-lymphoma syndrome, a chronic myeloproliferative disorder that frequently presents with eosinophilia and associated T-cell lymphoblastic lymphoma. The disease is aggressive and rapidly transforms to acute leukaemia, usually of myeloid phenotype. Currently, only allogeneic stem cell transplantation appears to be effective in eradicating or suppressing the malignant clone. To date, four gene fusions associated with distinct translocations have been described in EMS: the t(8;13)(p11;q12), t(8;9)(p11;q33), t(6;8)(q27;p11) and t(8;22)(p11q22) fuse ZNF198, CEP110, FOP and BCR, respectively, to FGFR1. The resulting fusion proteins have constitutive tyrosine kinase activity and activate multiple signal transduction pathways. These pathways and the fusion proteins are attractive targets for targeted signal transduction therapy.
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PMID:The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1. 1191 91

The 8p12 myeloproliferative syndrome is a rare, generally aggressive chronic myeloproliferative disorder (MPD). The hallmark of this MPD is the disruption of the FGFR1 gene, which encodes a tyrosine kinase receptor for members of the fibroblast growth factor family. In MPD cells FGFR1 is fused to several partners. The most frequent partner genes are BCR, CEP110, FOP, and ZNF198, localized on 22q11, 9q33, 6q27, and 13q12, respectively. We report here the tenth case of translocation (8;9)(p12;q33) in an acute myelomonocytic leukemia and provide a review of the literature that points to common syndrome features: the t(8;9)(p11;q33) MPD transforms rapidly, and always in myelomonocytic leukemia, with a possible B- or T-lymphoid involvement, which may include tonsil invasion. The FGFR1-MPD seems refractory to current chemotherapies and is not sensitive to imatinib. Currently, only the patients with bone marrow transplantation stand a chance of survival.
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PMID:Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110-FGFR1 fusion: report of a new case and review of the literature. 1809 25