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

Peripheral blood from a patient with acute myeloid leukaemia (AML) of M5 FAB classification, was shown to have mutations to both the N and K ras genes. Leucophoresed blood was separated on a discontinuous Percoll density gradient to provide fractions enriched for different cell lineages. DNA extracted from these fractions was amplified using the polymerase chain reaction (PCR) technique, and hybridized with oligonucleotide probes specific for the single base mutations previously demonstrated. The N-ras mutation was shown to be restricted to the blast and monocytic cell fractions, concordant with the FAB subtype of M5. The K-ras mutation, however, was present in all fractions, suggesting it had occurred in a multi-potential stem cell representing an earlier stage in the generation of the leukaemia, or possibly an incidental background phenomenon.
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PMID:Co-incident N and K ras gene mutations in a case of AML, restricted to differing cell lineages. 268 56

A high incidence of multiple primary neoplasms has been observed in our patients with ATL in comparison to persons with other forms of hematologic malignancy who we have observed during the past 24 years (1963-1985). Five of 15 patients with ATL (33.3%) have had at least one other associated neoplasm in comparison to only 44 of 1156 patients with other forms of hematological malignancy (3.8%). The incidence figures for secondary neoplasms associated with the other hematologic malignancies were 4.3% (16/370) for acute non-lymphocytic leukemia (ANLL), 2.2% (2/90) for acute lymphocytic leukemia (ALL), 4.8% (1/21) for acute unclassifiable leukemia, 2.2% (5/225) for chronic myelogenous leukemia, 4.7% (2/43) for chronic lymphocytic leukemia, 5.9% (8/136) for malignant monoclonal gammopathy and 3.7% (10/271) for malignant lymphoma. The incidence of multiple neoplasms in patients with ATL in comparison to those with other hematological malignancies was significant (p less than 0.01 or p less than 0.001). The neoplasms associated with ATL have been adenocarcinoma of the thyroid or lung, and squamous cell carcinoma of the larynx, lip or lung. We identified ATL-derived factor (ADF) in the cytoplasm of the secondary neoplasms of the ATL patients by means of indirect immunofluoroscopy and immunohistochemical techniques utilizing anti-ADF antibody. We also identified ras p21 products in these neoplasms by means of p21 ras monoclonal antibody studies. The possibility that HTLV-I was the cause of the secondary neoplasms thus was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on association between the ATL and the development of multiple malignant neoplasms--analysis of 1171 cases of hematological malignancies during the past 24 years]. 268 7

Some of the current critical issues in the tiazofurin treatment of end-stage leukemia were presented and discussed. 1. Tiazofurin infusions (daily X 10 to 15) provided remissions in 50% of end-stage leukemic patients. The remissions, of 1 to 10 months' duration, varied from antileukemic effect or hematologic improvement to complete response and complete remission. The total survival of the responding patients was from about 1 to 15 months. 2. Our administration of tiazofurin in a 60-min infusion by pump decreased the incidence and severity of toxicity. 3. It was shown that tiazofurin dose does not need to be escalated at each relapse. Depending on the biochemical and hematological response in this novel protocol, 2,200 to 4,400 mg/m2 tiazofurin appeared to be sufficient to provide remissions. 4. A new role was identified for allopurinol, originally given to decrease uric acid in the plasma. Allopurinol markedly increased plasma hypoxanthine concentrations which competitively inhibited the activity of the salvage enzyme, guanine phosphoribosyltransferase, in the blast cells. Thus, the elevated hypoxanthine plasma levels inhibited guanine salvage. To maintain high hypoxanthine levels allopurinol (100 mg) was given every 4 to 6 hr. This provided combination chemotherapy with tiazofurin which inhibited IMP dehydrogenase activity and blocked the de novo biosynthesis of guanylates in the blast cells. 5. Preliminary evidence was obtained in the patients that tiazofurin induced differentiation of the bone marrow. Recent studies also showed that tiazofurin down-regulated the expression of the c-Ki-ras oncogene in K562 erythroleukemic cells. Therefore, tiazofurin treatment provides an impact by chemotherapy, induced differentiation, and, if applicable, through down-regulation of the ras oncogene. 6. Novel aspects of tiazofurin treatment include rational targeting and a continuously monitored trial by measurement of the activity of IMP dehydrogenase and of GTP and TAD concentrations in blast cells and of tiazofurin and hypoxanthine in plasma. 7. Since tiazofurin has not yet achieved lasting remissions in patients nor terminal differentiation of leukemic cells it probably will be advantageous to combine tiazofurin with other drugs to provide synergism. In preclinical tissue culture studies in HL-60 cells synergy was observed with retinoic acid. This may be of interest because retinoic acid also caused differentiation and down-regulation of the myc oncogene.
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PMID:Critical issues in chemotherapy with tiazofurin. 269 55

The murine long-term bone marrow culture system which can support the almost infinite growth of normal B lineage cells was used to establish the experimental model for spontaneous B cell leukemogenesis. At the early phase of the culture, B cell differentiation with diversification of immunoglobulin genes was induced. However, the culture was finally captured by a single B cell clone which had the fastest growth rate. The B cell clone was strictly dependent on stromal cells for in vitro growth and did not generate leukemia when injected into syngenic mice. After up to a year of maintenance of the clone, the leukemic cells developed spontaneously. The leukemic cell line isolated in vivo retained the stromal cell-dependency, and further in vitro selection process was required to establish the stromal cell-independent leukemic cell line. These leukemic cell lines highly expressed c-myc and Ha-ras genes regardless of stromal cell-dependency. We detected no chromosomal aberrations accompanied with the process of leukemic transformation. Our results suggest that spontaneous neoplastic transformation of B cells in long-term bone marrow culture occurs in a stepwise manner.
Leukemia 1989 Apr
PMID:Stepwise progression of B cell malignancy occurred in a bone marrow stromal cell-dependent pre-B cell clone. 278 22

Transformation of a rat thyroid epithelial cell line (FRTL5-C12) with Kirsten and Harvey murine sarcoma viruses (carrying the ras oncogenes) results in elevated levels of three perchloric acid-soluble nuclear phosphoproteins. These three proteins are also induced to high levels in the PC-C13 thyroid epithelial cell line when transformed by the myeloproliferative sarcoma virus (carrying the v-mos oncogene) and when transformed by transfection with the c-myc proto-oncogene followed by infection with the polyoma leukaemia virus (PyMuLV) carry the polyoma middle T antigen gene. Neither c-myc or PyMuLV alone induced high levels of the three nuclear proteins. Untransformed thyroid fibroblasts have high levels of two of the three proteins and can be transformed by PyMuLV alone resulting in the appearance of the third protein. Transformation with Harvey sarcoma virus also results in the induction of the third protein. The three phosphoproteins have been purified by h.p.l.c. and shown to be related to the HeLa protein HMGI already described. The results of these studies indicate that elevated levels of these HMGI-like proteins are associated with neoplastic transformation and/or with an undifferentiated phenotype.
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PMID:Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle T genes. 282 Jul 15

A simple oncogene isolation was proved using the SD1-T rat embryonic cell line. The SD1-T cell line, which releases endogenous rat leukemia virus, was cocultured with (a) normal rat kidney cells transformed by cloned v-mos DNA, (b) the rat mammary tumor cell line (63SP), or (c) normal rat kidney cells transformed by 63SP DNA. Within 1 mo, oncogenic viruses were recovered from all three coculture supernatants. During this period, increase of oncogenic transcripts was observed in the cocultured cells. The oncogenic viruses appeared to contain the mos gene in cocultures (a) and ras-related sequences in cocultures (b) and (c). The emergence of virus containing mos from mos DNA-mediated normal rat kidney transformants demonstrated "rescue" of the active cellular oncogene by the rat leukemia virus. This coculture system seems to facilitate "rescue" of oncogenes functioning in the tumor and transformed cells.
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PMID:Production of recombinant rat viruses as a method of oncogene isolation in coculture medium. 282 37

Amphotropic murine leukemia virus pseudotypes of murine sarcoma viruses containing the ras or mos oncogenes were constructed to permit efficient introduction of the sarcoma virus genome into early-passage human umbilical vein endothelial cells. The resulting cell lines were morphologically and phenotypically unchanged, retaining properties characteristic of differentiated endothelial cells. For example, the cells in a Kirsten sarcoma virus-modified line were found to biosynthesize and secrete von Willebrand factor in both a constitutive and regulated manner, and they contained ultrastructurally identifiable Weibel-Palade bodies, an endothelial cell-specific organelle. In contrast to the parent cultures, sarcoma virus-modified cells were able to proliferate indefinitely in culture. Examination of both Kirsten sarcoma and Moloney leukemia virus-modified lines indicated that the immortalized cells retained a diploid female karyotype after over 18 months in culture. In addition, the sarcoma virus-modified cells were able to grow independently of added endothelial cell growth factor. This growth factor autonomy does not appear to be due to autocrine production of a biologically cross-reactive growth factor. These immortal, virus-modified endothelial cells express large amounts of sarcoma virus-specific mRNA but no detectable helper virus or transforming virus activity. This technique for immortalization of primary human cells without alteration of the differentiated characteristics of the cell type is readily applied to a variety of human cell types. Moreover, the ability to separate the immortalizing and transforming activities of viral oncogenes should provide further understanding as to mechanisms of oncogene action.
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PMID:Immortalization of human endothelial cells by murine sarcoma viruses, without morphologic transformation. 282 2

The expression of 8 protooncogenes was examined in different types of murine leukemia induced by Mazurenko virus. C-myc-specific RNA (2, 3 kb and 1.8 kb) was revealed only in tissues of mice with thymomas (T-cell leukemias) but not with generalized leukemias. 1.4 kb Ha-ras RNA transcripts were observed in all RNA species from leukemic mice. The highest expression of the above oncogenes was noted in thymus and lymph nodes, in spleen and liver the expression was lower. Ki-ras, abl, fos, myb, erb and B-lym-specific RNA expression was not observed in any of the tissues tested. The expression of C-myc RNA is believed to be the result of C-myc activation due to provirus integration.
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PMID:[Proto-oncogene expression in mouse leukemia induced by the Mazurenko virus]. 282 9

The effect of infecting fibroblasts with Kirsten murine sarcoma virus/murine leukemia virus (Ki-MSV/MLV) on constitutive and IFN-gamma-induced H-2 antigen expression was investigated. The fibroblasts used were two established cell lines (C3H10T1/2 and BALB/c3T3) and fresh embryo fibroblasts from C3H mice. Class I antigens were expressed constitutively by BALB/c3T3; infection with MLV, MSV or the two together had little effect on this constitutive expression. Class I antigens (H-2K, H-2D) were strongly induced on all three types of fibroblast by rIFN-gamma, and infection had little effect on this. None of the fibroblasts expressed constitutively detectable levels of class II antigen; however, C3H10T1/2 fibroblasts could be induced for both H-2A and H-2E by IFN-gamma. Infection of C3H10T1/2 with helper-free Ki-MSV, or MSV together with MLV, completely abolished this induction of class II antigens, while infection with MLV alone had little effect, implying that the abolition of class II induction was due to genomic regions of Ki-MSV not shared with Ki-MLV, probably the v-Ki-ras gene.
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PMID:Kirsten murine sarcoma virus abolishes interferon gamma-induced class II but not class I major histocompatibility antigen expression in a murine fibroblast line. 283 Dec 93

Transgenic mice harboring a c-myc gene subjugated to the immunoglobulin heavy chain enhancer offer a unique opportunity to investigate whether deregulated myc expression potentiates the transformation of B lymphoid cells by other oncogenes. By assessing colony formation in semi-solid medium, we have compared the potential of bone marrow cells from E mu-myc mice and their normal littermates for transformation by Harvey murine sarcoma virus and Abelson murine leukemia virus. E mu-myc bone marrow yielded more lymphoid colonies than normal marrow after infection with Harvey virus. The increased transformation frequency may reflect increased clonogenicity due to complementation between myc and ras and/or the increased number of pre-B cells in E mu-myc marrow. Surprisingly, however, the number of lymphoid colonies induced by Abelson virus was not enhanced. Our interpretation of these results is that the primary Abelson target is more primitive than the pre-B cells expressing the E mu-myc transgene and is therefore not present at increased frequency in the E mu-myc marrow. The cells from most virus-infected E mu-myc colonies failed to grow indefinitely when placed in liquid culture in the absence of a feeder layer. Thus expression of a deregulated c-myc gene together with either v-Ha-ras or v-abl does not ensure fully autonomous growth of early B lymphoid cells.
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PMID:Transformation of bone marrow cells from E mu-myc transgenic mice by Abelson murine leukemia virus and Harvey murine sarcoma virus. 284 Jun 24


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