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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A molecular clone containing part of the transforming gene from two human sarcoma cell lines, HT1080 and RD, has been obtained and shown to represent a new member of the human ras gene family. The transforming gene has undergone no major rearrangements and has not been amplified in either sarcoma cell line. The major transcript from the gene is 2,200 nucleotides long and is present at the same levels in both normal fibroblasts and tumour cells. The same gene is also activated in HL60, a promyelocytic leukaemia line and in SK-N-SH, a neuroblastoma line. The gene, N-ras, is located on chromosome 1.
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PMID:Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. 630 21

Five unrelated mouse tumours have been shown to carry activated transforming genes using the NIH/3T3 transfection assay. Three of these tumours, a T-cell lymphoma, a fibrosarcoma and a macrophage tumour, were found to carry an activated c-Ki-ras gene. A c-Ha-ras gene was shown to be activated in a myeloid leukaemia and a recently identified member of the 'ras' gene family, N-ras, was found to be activated in a lung carcinoma. The T-cell lymphoma, L5178Y-ES, is a more aggressively growing metastatic variant which arose spontaneously from the parental tumour, L5178Y-E. Although DNA from both parental and variant tumours was shown to transfer a genetic marker to recipient cells equally well, only the metastatic variant carried an activated c-Ki-ras gene detectable by transfection. The altered growth behaviour of the L5178Y-ES cells may therefore be the result of the spontaneous activation of the c-Ki-ras gene after the lymphoma cells had already become tumorigenic.
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PMID:Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma. 632 95

Human tumour cell lines of various histological origin contain genes that can transform NIH 3T3 cells in culture. Most frequently the gene is an activated K-ras gene, more rarely an activated H-ras gene, and sometimes the recently discovered N-ras. Other transforming genes, distinct from ras, have been found in B- and T-cell leukaemias. Since most of the transforming genes have been identified in cell lines, it is still unclear at what stage the genes become activated. We have therefore initiated a study to determine if the presence of a transforming gene correlates with the clinical course of a malignant disease. Here we demonstrate the presence of a transforming N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia at the outbreak of the acute disease phase. Fibroblast DNA from the same patient was not transforming. In contrast to HL-60 cells, no alteration of the myc gene was detected.
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PMID:Activation of N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia. 658 53

The oncogene of the HL-60 human promyelocytic leukemia cell line has been passed serially through NIH/3T3 mouse fibroblasts. Oncogene-specific probes prepared from the resulting tertiary transfectants by molecular cloning have been used to show that loss of the transfected oncogene from NIH/3T3 cells correlates with reversion to nontransformed morphology. Analysis of cells transfected by the oncogenes of other tumors and tumor cell lines indicates that the transforming gene of the HL-60 leukemia cell line is closely related to oncogenes of a Burkitt's lymphoma, an acute myelogenous leukemia, an adenocarcinoma of the colon, a neuroblastoma, and two sarcomas. This oncogene is distantly related to the viral oncogenes of Kirsten and Harvey sarcoma viruses. It has been termed N-ras. The active N-ras oncogene coexists with altered versions of the myc oncogene in the HL-60 and AW Ramos human tumors. This suggests a multistep mechanism involving both ras and myc genes in the creation of these tumors.
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PMID:The HL-60 transforming sequence: a ras oncogene coexisting with altered myc genes in hematopoietic tumors. 668 94

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.
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PMID:Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan. 749 45

Activation of the N- and K-ras proto-oncogenes is the most common molecular abnormality in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In retrospective studies, approximately 3-36% of MDS patients were reported to harbor a mutated ras proto-oncogene, with some series suggesting the presence of ras-mutations are associated with progressive disease and a poor prognosis. Since hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) are currently used for therapy in MDS but may stimulate the proliferation of leukemic cells, we assessed the frequency and significance of ras mutations in 27 MDS patients, 15 of whom underwent G-CSF therapy. Patients were analyzed for the presence of mutations in codons 12, 13, and 61 of the N- and K-ras proto-oncogenes. Only three patients (11%, two refractory anemia with excess of blasts (RAEB), one RAEB in transformation (RAEB-T)) harbored activated ras oncogenes with the mutations localized in N-ras codons 12 and 61. Patients were followed for periods of up to 4 years or until death supervened. Patients exhibiting ras mutations were no more likely to develop AML compared to ras-negative patients (1/3 vs. 10/24) or to have decreased survival (p = 0.64). These data indicate that, in this group of MDS patients, ras mutations do not appear to correlate with a poor prognosis, and do not adversely interact with exogenously administered G-CSF.
Leukemia 1994 Apr
PMID:Mutations in the ras proto-oncogenes in patients with myelodysplastic syndromes. 751 75

Intravenous injections of 7,12-dimethylbenz[a]anthracene (DMBA) induce erythroblastic leukemia (erythroleukemia) with No.2 trisomy in Long-Evans rats. Activation of some oncogenes such as abl and Ha-ras has been reported to occur in relation to the secondary chromosomal translocations. In the present studies, a consistent type of mutation, A to T transversion in codon 61 of N-ras gene, was found in all of 6 cultured leukemia cell lines and 5 primary leukemias induced by DMBA. The N-ras mutation was also found in bone marrow cells of 2 out of 8 preleukemias. On the contrary, no mutation was observed in Ha- and Ki-ras genes in all leukemias and preleukemias. The consistent occurrence of above N-ras mutation in leukemias indicates that it plays an important role in DMBA-leukemogenesis.
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PMID:N-ras mutation in 7,12-dimethylbenz[a]anthracene (DMBA)-induced erythroleukemia in Long-Evans rats. 775 91

Specific chromosomal aberrations and point mutations of the N-ras proto-oncogene are characteristic genetic alterations in acute leukaemias. However, the relationships between these two different genetic changes are unclear. Here we have determined the order of genetic events in a patient with acute myeloid leukaemia characterized by trisomy 8 and a point mutation of N-ras at codon 12 (N12-cys) and codon 61 (N61-his). 30 colonies obtained by in vitro clonogenic assay of leukaemic cells from a patient with AML were individually analysed for the presence of trisomy 8 and each of two different N-ras mutations by fluorescence in situ hybridization (FISH) and the polymerase chain reaction (PCR). Trisomy 8 was detected in 25/26 evaluable colonies. 19/26 colonies contained the N12-cys mutation. The N61-his mutation was not detected in any of the colonies obtained. All the colonies with the N12 cys mutation were also trisomic from chromosome 8, whereas 6/25 colonies with trisomy 8 had no N-ras mutation. These data suggest that trisomy 8 was acquired before N12 cys mutation in the pathogenesis of this leukaemia and that two genetic events can co-operate within a single subclone.
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PMID:Sequential acquisition of trisomy 8 and N-ras mutation in acute myeloid leukaemia demonstrated by analysis of isolated leukaemic colonies. 780 79

Oncogene mutations are frequently found in several tumour types and, among these, point mutations of the ras gene are particularly significant. A predominance of N-ras mutations has been found in the bone marrow DNA of patients with myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML). On the other hand, increased levels of plasma DNA have previously been observed in patients suffering from various malignant diseases. In the present work we have investigated, by polymerase chain reaction (PCR), point mutations of the N-ras gene in the DNA of plasma, blood cells and bone marrow of 10 patients suffering from AML or MDS. The different ras mutations detected in five cases were always present in the plasma DNA while sometimes absent in the DNA of peripheral blood cells or bone marrow. This indicates that a bone marrow biopsy or aspiration does not necessarily contain all the malignant clones involved in the disease. Plasma could thus prove to be an easily accessible and useful material for detection and monitoring of myeloid disorders.
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PMID:Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. 791 71

To determine the incidence and prognostic significance of mutation in the N-ras gene in de novo acute myeloid leukemia (AML) we performed an analysis of bone marrow smears from 219 patients with de novo AML treated between 1984 and 1986 and followed for at least six years. DNA extracted from bone marrow smears taken at diagnosis was screened for the presence of mutations in codons 12 and 13 of exon 1 by using the polymerase chain reaction to insert an Hph1 restriction enzyme site into DNA. Presumptive mutations were confirmed by direct sequencing. Mutations were detected in a total of 26 patients (12%); in nine patients (4%) in codon 12 only, in ten patients (5%) in codon 13 only, and in seven patients (3%) in both codons. Mutations in codon 12 or codon 13 were not associated with any clinical features. Mutations in codon 12 had no prognostic significance but mutations in codon 13 were associated with an increased remission rate, a more durable remission, and a significantly prolonged survival which appeared to be independent of other prognostic factors.
Leukemia 1994 Oct
PMID:The incidence and prognostic significance of mutations in codon 13 of the N-ras gene in acute myeloid leukemia. 793 63


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