Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The FMS gene encodes the functional cell surface receptor for colony-stimulating factor 1, the macrophage- and monocyte-specific growth factor. Codons 969 and 301 have been identified as potentially involved in promoting the transforming activity of FMS. Mutations at codon 301 are believed to lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. The tyrosine residue at codon 969 has been shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. This study reports on the frequency of point mutations at these codons, in vivo, in human myeloid malignancies and in normal subjects. We studied 110 patients [67 with myelodysplasia (MDS) and 48 with acute myeloblastic leukemia (AML)], 5 patients being studied at the MDS and the later AML stage of the disease. There was a total incidence of 12.7% (14/110) with mutations in codon 969 and 1.8% (2/110) with mutations in codon 301. Two patients had mutations in the AML stage of the disease but not in the preceding MDS and one had a mutation in the MDS stage but not upon transformation of AML. This is consistent with the somatic origin of these mutations. FMS mutations were most prevalent (20%) in chronic myelomonocytic leukemia and AML type M4 (23%), both of which are characterized by monocytic differentiation. One of 51 normal subjects had a constitutional codon 969 mutation, which may represent a marker for predisposition to myeloid malignancy.
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PMID:FMS mutations in myelodysplastic, leukemic, and normal subjects. 240 20

Several proto-oncogenes have been reported to be expressed in normal and malignant hematopoietic cells. Since these studies have been done almost exclusively by Northern and dot-blot analyses using mixed populations of cells, any conclusions concerning quantitative changes in gene expression are difficult to document. We have developed a rapid and sensitive RNA-in situ hybridization technique permitting detection of as few as 5 copies of mRNA per individual cell. Using this technique we have studied the expression levels of several oncogenes including MYC, SIS, FMS, p53, FOS and RAF in both normal hematopoietic cells and bone marrow (BM) cells obtained from acute myelogenous leukemia (AML) patients at presentation, at relapse and in complete remission (CR). Two of these oncogenes, MYC and SIS, are expressed at levels at least 2-5-fold higher in hematopoietic cells obtained from leukemia patients than in any normal hematopoietic cell examined, including cells obtained from regenerating bone marrow. The proportion of abnormal cells correlated well with the percentage of blast cells determined by morphological examination. In 7 out of 10 AML patients in morphological remission, a subpopulation of cells is detectable with abnormally high levels of MYC and/or SIS mRNA. These high levels of MYC expression are similar to those found in BM cells obtained from AML patients at presentation or relapse, but the percentage of cells with this abnormality is generally much lower. Continued follow-up of these patients has shown that 5 of them relapsed within 8 months. At this time, none of the 3 patients which were negative for MYC overexpression has relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of minimal residual disease in acute myelogenous leukemia by RNA-in situ hybridization. 265 88

By in situ chromosomal hybridization, the GM-CSF and FMS genes were localized to human chromosome 5 at bands q23 to q31, and at band 5q33, respectively. These genes encode proteins involved in the regulation of hematopoiesis, and are located within a chromosome region frequently deleted in patients with neoplastic myeloid disorders. Both genes were deleted in the 5q-chromosome from bone marrow cells of two patients with refractory anemia and a del(5)(q15q33.3). The GM-CSF gene alone was deleted in a third patient with acute nonlymphocytic leukemia (ANLL) who has a smaller deletion, del(5)(q22q33.1). Leukemia cells from a fourth patient who has ANLL and does not have a del(5q), but who has a rearranged chromosome 5 that is missing bands q31.3 to q33.1 [ins(21;5)(q22;q31.3q33.1)] were used to sublocalize these genes; both genes were present on the rearranged chromosome 5. Thus, the deletion of one or both of these genes may be important in the pathogenesis of myelodysplastic syndromes or of ANLL.
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PMID:Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. 348 37

The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, we localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5)(q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 [ins(21;5)(q22;q31.3q33.1)] resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33.1. Thus, a small segment of chromosome 5 contains GM-CSF (the gene encoding the granulocyte-macrophage CSF), CSF-1, and FMS, which encodes the CSF-1 receptor, in that order from the centromere; this cluster of genes may be involved in the altered hematopoiesis associated with a deletion of 5q.
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PMID:Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. 349 6

The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).
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PMID:The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q. 349

Our chemoimmunotherapy study shows significantly longer remission and survival in acute myelocytic leukemia (AML) patients who have been immunized with neuraminidase-treated allogeneic myeloblasts as compared to patients who received chemotherapy alone or neuraminidase-treated myeloblasts plus MER. MER impairs the immunotherapeutic effectiveness of neuraminidase-treated allogeneic myeloblasts in AML patients. The in vivo and in vitro immunologic status in each arm of the protocol correlate well with the duration of remission and survival of the patient.
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PMID:Therapeutic effectiveness of neuraminidase-treated allogeneic myeloblasts as immunogen in acute myelocytic leukemia. 680

The region surrounding the human acidic fibroblast growth factor (FGF1) locus on chromosome 5q31 is of particular interest since it represents a critical region consistently lost in acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS) patients who have a demonstrable deletion of the distal portion of the long arm of chromosome 5. It is proposed that an ANLL/MDS leukemia suppressor gene resides on 5q31. We have previously shown that the gene is most likely localized between FGF1 and PDGFRB/CSF1R loci. The region has also been linked to at least four other genetic diseases, Treacher Collins syndrome, diastrophic dysplasia, limb-girdle muscular dystrophy, and an autosomal dominant deafness, by linkage analysis. Here, we describe yeast artificial chromosomes (YAC) spanning 450 kb around the FGF1 gene. Six YAC clones were isolated from a human YAC library and their restriction enzyme maps were determined. The overlap of the clones with each other and with FGF1 cosmid and phage clones was characterized. Three of the YAC clones were found to contain the entire FGF1 gene, which spans more than 100 kb. Proximal and distal ends of several of these YAC clones were isolated for further overlap cloning. The proximal ends of both Y2 and Y4 were localized to previously isolated FGF1 DNA by sequence analysis. The distal ends of these two clones also hybridized to a human-hamster hybrid containing chromosome 5 as the only human genetic material. These results suggest that these YAC clones represent colinear DNA around the FGF1 locus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Construction of a yeast artificial chromosome contig encompassing the human acidic fibroblast growth factor (FGF1) gene: toward the cloning of the ANLL/MDS tumor-suppressor gene. 751 71

The class I receptor tyrosine kinase (RTK) HER2 is an oncoprotein that is frequently involved in the pathogenesis of tumors of epithelial origin. Here we report mRNA expression in peripheral blood and bone marrow cells from healthy donors in hematopoietic cell lines and leukemic blasts from patients with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and chronic myeloid leukemia (CML). However, cell surface expression of HER2 protein (p185HER2) was found exclusively on a subset of leukemic cells of the B-lymphoblastic lineage. p185HER2 expression was found on blasts in 2 of 15 samples from infants, 9 of 19 samples from adult patients with C-ALL (CD19+CD10+), and 1 of 2 samples from patients with pro-B ALL (CD19+CD10-), whereas none of the leukemic cells from patients with AML (0/30), T-ALL (0/7), CLL (0/5) (CD19+CD5+), or CML in chronic and accelerated phase (0/5) or in blast crisis with myeloid differentiation (0/14) were positive for p185HER2. However, cells from 3 of 4 patients with CML in B-lymphoid blast crisis (CD19+CD10+) expressed high levels of p185HER2, which was also found on the surface of the CML-derived B-cell lines BV-173 and Nalm-1. Our study shows p185HER2 expression on malignant cells of hematopoietic origin for the first time. Aberrant expression of this oncogenic receptor tyrosine kinase in hematopoietic cell types may be an oncogenic event contributing to the development of a subset of B-lymphoblastic leukemias.
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PMID:The receptor tyrosine kinase p185HER2 is expressed on a subset of B-lymphoid blasts from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia. 754 46

FLT4 is a recently cloned receptor tyrosine kinase cDNA, which is characterized by seven immunoglobulin-like loops in its extracellular domain. We have previously mapped the FLT4 gene to chromosome segment 5q33-qter using somatic cell hybrids. Here we have refined the localization to band 5q35 by fluorescence in situ hybridization and show that the gene is translocated to chromosomes 2 and 6 in the t(2;5)(p23;q35) and t(5;6)(q35;p21) translocations, respectively, of Ki-I-positive lymphomas, as well as to chromosome 3 in the t(3;5)(q25.1;q34) translocation, which is occasionally found in myelodysplastic syndromes and acute myeloid leukemia. No evidence was obtained for a rearrangement or deregulation of the translocated FLT4 gene. We further show that abundant FLT4 mRNA expression occurs only in erythroid and megakaryoblastoid cell lines among nine leukemia cell lines studied.
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PMID:FLT4 receptor tyrosine kinase gene mapping to chromosome band 5q35 in relation to the t(2;5), t(5;6), and t(3;5) translocations. 768 67

Point mutations at codons 301 and 969 of the FMS proto-oncogene have been reported in both myelodysplasia (MDS) and acute myeloid leukaemia (AML). We report here the incidence of such mutations in patients at risk of developing secondary MDS and AML. Peripheral blood DNA from 70 patients in remission from lymphoma was screened for mutations by oligonucleotide (ONH) using mutant specific probes. Codon 969 mutations were detected in 11 of the 70 (15.7%) cases. No codon 301 mutations were detected. Five of these mutations were confirmed using an independent technique (single nucleotide primer extension analysis, SNPE) and a further mutation was detected in a single patient using single-stranded conformational polymorphism analysis (SSCP). No codon 969 mutations were detected in 62 lymphoma biopsy specimens from these patients or from three patients with detectable FMS mutations where pre-therapy marrow was investigated by ONH. No mutations at either codons 301 or 969 were detected by ONH in 61 normal controls. Somatic mutations at codon 969 of the FMS gene occur commonly following cytotoxic therapy for lymphoma and their detection indicates the presence of a clonally expanded population of abnormal cells.
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PMID:FMS mutations in patients following cytotoxic therapy for lymphoma. 776 31


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