Humans ; Myeloproliferative Disorders ; genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder that occurs in either an inherited or a sporadic manner. KS results from failed embryonic migration of GnRH-1 neurons from the nasal placode to the hypothalamus, due to the abnormal development of olfactory nerves and bulbs. Hypogonadotropic hypogonadism is related to GnRH deficiency, and anosmia is associated with the absence or hypoplasia of olfactory bulbs and tracts. KS patients can also present some non-reproductive or non-olfactory anomalies in addition to the above typical symptoms. For the high complexity of the molecular genetic mechanism of KS, to date, only 6 KS-related genes have been identified. The KAL1 gene is responsible for the X chromosome-linked recessive form of KS, while the fibroblast growth factor receptor 1 (FGFR1/KAL2) and fibroblast growth factor 8 (FGF8/KAL6) genes are related to the autosomal dominant form of the disease. However, the mutations in these 6 genes account for only about 25 - 30% of all KS cases, which suggests that other pathogenic genes involved in KS remain to be discovered. This article presents an overview on the studies of the pathogenic genes, clinical diagnosis and treatment of KS.
Extracellular Matrix Proteins ; genetics ; Humans ; Kallmann Syndrome ; genetics ; Mutation ; Nerve Tissue Proteins ; genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

The 8p11 myeloproliferative syndrome (EMS) is named as stem cell leukemia/lymphoma syndrome, and is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase gene on chromosome 8p11-12. EMS is a syndrome characterized by peripheral blood leucocytosis with eosinophilia, myeloid hyperplasia of bone marrow, and T-cell lymphoblastic leukemia/lymphoma. Clinically, EMS is an aggressive disease with a short chronic phase before rapid transformation into acute leukemia. Its prognosis is poor. The only curative option for patients with EMS at this time appears to be bone marrow or stem cell transplantation. At the molecular level, all cases carry a chromosomal abnormality involving the FGFR1 gene at chromosome 8p11. The novel chimeric proteins foster dimerization and ligand-independent activation of FGFR1 tyrosine kinase, subsequently promoting activation of downstream pathways involved in proliferation and malignant transformation of cells. Currently, 13 translocations and 1 insertion have been identified. Here, the current review mainly focuses on molecular genetic features, pathogenic mechanisms and therapy of EMS.
Chromosomes, Human, Pair 8 ; Humans ; Myeloproliferative Disorders ; classification ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

OBJECTIVE: To study the potential significance and clinical application of FGFR1 gene abnormality in the diagnosis, clinical features, pathological mechanism and treatment in hematological tumors. METHODS: Clinical data of total of 29 patient with chromosome of 8 short arm (8P) abnormality who had more comprehensive medical history from 2013 to 2018 were collected. The karyotype analysis of bone marrow chromosomes in patients was carried out by using chromosome R band banding technique. FGFR1 gene was detected by using fluorescence in situ hybridization (FISH). RESULTS: Seven cases of FGFR1 gene abnormalities were decteted, including 3 cases of FGFR1 gene amplification, 2 cases of translocation, and 2 cases of deletion. Five patients with FGFR1 gene amplification or deletion not accompaned with eosinophilia, moreover the chromosome was a complex karyotype with poor prognosis; Two cases of FGFR1 gene translocation were non-complex chromosomal translocation and one of which survived for 6 years after bone marrow transplantation, the other chromosome karyotype showed no rearrangement of 8 short arm. However, FGFR1 gene rearrangement was confirmed by FISH analysis, which was a rare insertional translocation. CONCLUSION FGFR1 gene amplification or deletion often occur in cases with complex karyotype, which not accompany eosinophilia, moreover have poor prognosis. The patients with FGFR1 gene translocation accompany eosinophilia which is consistent with the clinical characteristics of myeloid / lymphoid neoplasms with FGFR1 abnormality. Karyotype analysis combined with FISH method can improve the detection of abnormal clones.
Chromosome Aberrations ; Hematologic Neoplasms ; genetics ; metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Translocation, Genetic

Animals ; Eosinophilia ; genetics ; pathology ; Gene Rearrangement ; Humans ; Lymphoma ; genetics ; pathology ; Myeloproliferative Disorders ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Receptor, Platelet-Derived Growth Factor beta ; genetics

Adult ; Aged ; Female ; Fibroblast Growth Factor 1 ; genetics ; Fibroblast Growth Factor 2 ; genetics ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; analysis ; Receptor Protein-Tyrosine Kinases ; genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptors, Fibroblast Growth Factor ; genetics

Kallmann syndrome (KS) is a rare hereditary disease. It is characterized by hypogonadotrophic hypogonadism in association with anosmia or hyposmia. At present, three modes of inheritance and genes related to KS have been identified. This review focuses on the clinical diagnosis and advances in the studies of the pathogenesis gene for Kallmann syndrome.
Diagnosis, Differential ; Extracellular Matrix Proteins ; genetics ; Humans ; Kallmann Syndrome ; diagnosis ; genetics ; therapy ; Male ; Nerve Tissue Proteins ; genetics ; Rare Diseases ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

DNA-Binding Proteins ; genetics ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Transcription Factors ; genetics

OBJECTIVE To explore the clinical and laboratory features of a patient with 8p11 myeloproliferative syndrome (EMS) and CEP110-FGFR1 fusion. METHODS Combined bone marrow cytology, fluorescence in situ hybridization, fusion gene detection was used to analyze the patient. RESULTS Clinically, the patient had many features similar to those with chronic myelomonocytic leukemia, which included hyperleukocytosis, marked eosinophilia, monocytosis, myeloid hyperplasia and hyperplasia. Fluorescence in situ hybridization analysis for FGFR1 gene rearrangement was positive. Further study of the mRNA also confirmed an in-frame fusion between exon 38 of the CEP110 gene and exon 9 of FGFR1 gene. CONCLUSION EMS with CEP110-FGFR1 fusion is a very rare and distinct myeloproliferative neoplasm. FISH and molecular studies may improve its diagnosis.
Cell Cycle Proteins ; genetics ; Chromosomes, Human, Pair 8 ; Female ; Humans ; Middle Aged ; Myeloproliferative Disorders ; genetics ; Oncogene Proteins, Fusion ; genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

This study was aimed to clone the gene coding mouse fibroblast growth factor receptor-1 (fgfr1), to construct the recombinant lentiviral vector of truncated form fgfr-1 (Δfgfr1) carrying enhanced green fluorescence protein (EGFP) and to investigate its expression in eukaryotic cells (293FT cells). The full length fgfr1 gene was cloned by RT-PCR using brain tissue of BALB/c fetal mouse as template and inserted into PCR-Blunt vector, a truncated fgfr1 fragment was produced by site-directed mutagenesis for deleting intracellular phosphorylated domain, then was subcloned into a lentiviral vector and cotransfected into 293FT packaging cells together with envelope plasmid and packaging plasmid by lipofectamine 2000. Viruses were gathered and concentrated using ultracentrifuge, and then transfected into 293FT cells. Expression of EGFP was detected by fluorescent microscopy and flow cytometry (FCM), and the truncated FGFR1 protein was detected by Western blot. The results demonstrated that mouse fgfr1 gene was cloned and the lentiviral expression vector LV-IRES-EGFP-Δfgfr1 and control vector LV-IRES-EGFP were successfully constructed. The lentiviral particles were correctly packaged, and the virus titers were above 10(8) TU/ml in the supernatant after concentration. Expression of EGFP was detected by fluorescent microscopy in 293FT cells post transfection, and the transfection efficacy was > 95% determined by FCM. Expression of FGFR1 protein detected by Western blot was significantly higher than that in control group. It is concluded that the truncated gene fgfr1 along with the gene coding EGFP is successfully inserted into a lentiviral vector to construct a recombinant lentiviral vector, which can be expressed in eukaryotic cells.
Animals ; Cell Line ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Mice ; Mice, Inbred BALB C ; Plasmids ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Recombinant Fusion Proteins ; genetics ; Transfection