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)

Thirty samples of cells from twenty-one cases of chronic lymphocytic leukemia (CLL) were transfected with myc and/or ras. Transformation, as assessed by growth in liquid culture and change in morphology, occurred in only one case. Colony culture in semi-solid media, however, does not occur with these cells. It would appear that the neoplastic genotype of CLL cells does not predispose the cells to readily transform, even with transfection with these two oncogenes.
Leukemia 1992
PMID:Transfection of chronic lymphocytic leukemic cells with myc and ras. 160 24

The tumor suppressor gene p53 has been shown to be mutated in 50% of acute lymphoblastic T-cell-leukemia (T-ALL) cell lines, all of which were established from T-ALL cases in relapse. In these lines both alleles of the p53 gene were independently affected by point mutation. In contrast, in human solid tumors possessing a mutated p53 allele, the second wild-type p53 suppressor allele is often lost by deletion rather than altered by mutation. This suggests that in T-ALL cell lines, the product encoded by the second mutated allele provides the cells with an additional oncogenic stimulus, beyond the loss of suppressive activity. While different p53 mutations have been shown to possess differential oncogenic potential in the p53 plus ras cotransformation assay, in T-ALL cells different mutations may in addition possess distinct functions, further contributing to the tumorigenic phenotype.
Leukemia 1992
PMID:Role of the p53 tumor suppressor gene in the pathogenesis and in the suppression of acute lymphoblastic T-cell leukemia. 160 34

Cytogenetic analysis of germ cell tumors (GCTs) has identified i(12p) as a specific cytogenetic abnormality identified in more than 80% of GCTs, present in all histologies, in primary and metastatic lesions, in testicular and extragonadal presentations, and in ovarian and sex cord stromal tumors. Other nonrandom numeric and structural chromosomal abnormalities have also been identified. Oncogene studies suggest a potential role for n-ras mutations in GCT transformation. The role of loss of tumor suppressor genes and increased genomic dosage of growth promoter genes remain areas of great interest. Leukemias and differentiated malignancies that arise in the setting of GCT appear to be clonally derived from GCT cells, with evidence of karyotypic progression and acquisition of other tumor-specific cytogenetic markers. Identification of i(12p) in poorly differentiated midline carcinomas of uncertain histogenesis can assist in the diagnosis of GCT. The presence of three or more copies of 12p may predict resistance to chemotherapy and portend a higher likelihood of treatment failure. Future cytogenetic studies in GCT promise to provide insight into the biology and treatment of all solid tumors, because GCTs are a model of chemotherapeutic responsiveness, cellular differentiation, and tumor clonal evolution.
 ...
PMID:Genetic analysis of germ cell tumors: current progress and future prospects. 166 44

The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degrees of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protooncogenes such as ras and fms have also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodysplastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients.
 ...
PMID:Recent advances in biology and treatment of myelodysplasia. 171 May 5

Seven tumors independently derived from a v-Ha-ras-expressing pre-B cell line were examined to determine the oncogene activations cooperating with v-Ha-ras in in vivo tumor progression. The pre-B cell line was generated by infection with Moloney murine leukemia virus (MoMuLV) and a MoMuLV-derived recombinant expressing v-Ha-ras. Two of seven tumors possessed a MoMuLV integration immediately upstream and in reverse transcriptional orientation to c-myc. This correlated with a 3-fold increased level of c-myc mRNA. Two other tumors displayed elevated c-myc mRNA levels, although the mechanism of enhanced expression was unclear. Thus the tumor progression of a v-Ha-ras-expressing murine pre-B cell line selects for the activation of c-myc.
 ...
PMID:Tumorigenesis of a v-Ha-ras-expressing pre-B cell line selects for c-myc activation. 171 20

Expression of the ras proto-oncogene mRNA in human myeloblastic leukemia (ML-1) cells was analyzed as a function of cDNA amplification by polymerase chain reaction (PCR). By using a pair of oligonucleotides that flank exon-2 from opposite strands (5' and 3') of H-ras cDNA for PCR amplification, ML-1 cells were found to express a 112 bp segment of the ras transcript. A rapid decline in the expression of this transcript was seen in cells treated with heptachlor, a chlorinated hydrocarbon insecticide. Expression of the same ras segment was not affected by treatment of ML-1 with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, addition of serum to quiescent, heptachlor-treated cultures of ML-1 cells inhibited the effect of heptachlor and restored the expression of the ras protooncogene mRNA.
 ...
PMID:The effect of the insecticide heptachlor on ras proto-oncogene expression in human myeloblastic leukemia (ML-1) cells. 177 36

Seventy five radiation-related leukemia patients in Hiroshima including 16 patients exposed to more than one Gray were cytogenetically examined. Statistical analysis of data on the frequencies of chromosomal aberrations in the survivor groups according to bone marrow doses by DS86 estimation revealed that the heavily exposed group tended to have significantly higher aberration rates compared to the non-exposed group. Furthermore, the chromosomal aberrations in the survivors were observed to be of a more complex nature and had the characteristic findings of secondary leukemia. These observations therefore suggest that patients with a history of heavy exposure to atomic bomb radiation had leukemic cells originating from a stem cell which had been damaged by irradiation at the time of the bombing as well as cells involved in complex chromosome abnormalities. Molecular biologic studies on ras genes in acute and chronic leukemias and the bcr gene in chronic myelocytic leukemia were performed in exposed and non-exposed groups. So far, no distinctive differences have been observed in the frequency and sites of point mutations in N- and K-ras genes or in the rearrangement of the bcr gene. Further, retrospective analysis using DNA from leukemia patients who developed this disease in the early period from atomic bomb radiation exposure would be useful for the elucidation of the mechanisms of radiation-induced leukemia.
 ...
PMID:Cytogenetic and molecular changes in leukemia among atomic bomb survivors. 182 62

In the 2H3 subline of rat basophilic leukemia cells (RBL-2H3), IgE receptor cross-linking stimulates a signal transduction pathway that leads to the secretion of histamine, serotonin, and other inflammatory mediators; the assembly of F-actin; and the transformation of the cell surface from a microvillous to a lamellar or ruffled architecture. We report here that 20 h incubation of RBL-2H3 cells with 10 microM lovastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG CoA reductase), inhibits both the secretory and morphologic responses to IgE receptor cross-linking. Ag-induced Ca2+ mobilization, determined from the influx and efflux of 45Ca2+, and Ag-induced 1,4,5-inositol trisphosphate production are also inhibited in lovastatin-treated RBL-2H3 cells. Under the same conditions, lovastatin does not alter cell proliferation or IgE receptor expression, and it causes only a small impairment of responses initiated by drugs that bypass the earliest steps in the receptor-activated transduction pathway (ionomycin-induced secretion and PMA-induced membrane ruffling). Receptor-mediated Ca2+ mobilization, secretion, and ruffling are all restored by 0.5- to 4-h incubation of lovastatin-treated cells with mevalonic acid, the product of HMG CoA reductase and the first committed intermediate of the isoprenoid biosynthetic pathway. In contrast, dolichol and cholesterol, which are synthesized from products of the isoprenoid pathway, do not restore receptor-activated responses. These data implicate an isoprenoid pathway intermediate in an early step in the IgE receptor-activated signal-transduction sequence. We postulate that this intermediate is required for a newly described post-translational modification of proteins, their post-synthetic isoprenylation. The substrates for this modification include the ras family of GTP-binding proteins and the gamma subunits of the heterotrimeric guanine nucleotide-binding protein.
 ...
PMID:Role of isoprenoid metabolism in IgE receptor-mediated signal transduction. 182 87

More than thirty small guanine nucleotide-binding proteins related to the ras-encoded oncoprotein, termed Ras or p21ras, are known. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down-regulation of the active GTP-bound form. For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling. We have purified a GAP protein for p21rho, which is involved in the regulation of the actin cytoskeleton. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr (breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome-positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n-chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21rac. This result suggest that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia.
 ...
PMID:Bcr encodes a GTPase-activating protein for p21rac. 190 16

N-ras gene activation occurs via single base substitutions in codons 12, 13, and 61. We have developed a rapid screening method, termed allele specific restriction analysis (ASRA), for detection of N-ras mutations at these three critical codons in acute myeloid leukemia (AML). Patient DNA samples are amplified by the polymerase chain reaction (PCR) by using primers that induce restriction sites in normal but not mutant N-ras alleles. We have used ASRA to identify 5 point mutations in four out of 19 patients at initial presentation of de novo AML. Three patients had one mutation at codon 12, 13, or 61 respectively, while a fourth patient had concurrent mutations at codons 12 and 13. N-ras mutations were more common in patients over 65 years of age (P less than 0.04), but did not correlate with FAB classification, attainment of complete remission, disease free survival, or overall survival. ASRA can also be used as the first step in a more sensitive approach to the detection of ras mutations. When ASRA was combined with allele specific oligonucleotide (ASO) hybridization the sensitivity and specificity of these assays were increased. This allowed identification of additional low level mutations in two patients. The data presented here constitute the first complete analysis of N-ras mutations in leukemia by ASRA and include the first identification of three concurrent N-ras mutations in a single leukemic patient. By facilitating sensitive sequential studies, ASRA should contribute to our understanding of the role of N-ras mutations in leukemogenesis.
 ...
PMID:Analysis of N-ras gene mutations in acute myeloid leukemia by allele specific restriction analysis. 195 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>