BLYM; avian lymphoma virus-derived transforming sequence (1p32)

Gene Summary

Gene:BLYM; avian lymphoma virus-derived transforming sequence
Summary: BLYM is a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymphomas. The gene is homologous by molecular hybridization with the Blym-1 transforming gene isolated from chicken B-cell lymphoma DNA and is not homologous with 12 retroviral transforming genes including MYC and RAS. Studies have found that avian lymphoma virus-derived transforming sequence has sequence homology to transferrin and suggested that its transforming gene products may function via a pathway related to transferrin.
Databases:OMIM, HGNC, GeneCard, Gene
Updated:14 December, 2014

Cancer Overview

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Publications Per Year (1989-2014)
Graph generated 14 December 2014 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Mice, Inbred Strains
  • Autoradiography
  • Genes, Dominant
  • Chromosome Aberrations
  • Translocation
  • Nucleic Acid Hybridization
  • Immunoglobulins
  • Oncogenes
  • Chickens
  • Lymphoma
  • Herpesvirus 4, Human
  • Repetitive Sequences, Nucleic Acid
  • Leukaemia
  • Proto-Oncogenes
  • Viral Proteins
  • T-Lymphocytes
  • Messenger RNA
  • Amino Acid Sequence
  • Transformation, Genetic
  • Cancer DNA
  • Chromosome 3
  • Chromosome Disorders
  • Karyotyping
  • Neoplastic Cell Transformation
  • Base Sequence
  • Chromosome 1
  • Chromosome Mapping
  • Cell Line
  • Transferrin
  • Receptors, Transferrin
  • Cultured Cells
  • Burkitt Lymphoma
  • Cloning, Molecular
  • DNA Restriction Enzymes
  • Cancer RNA
  • Meningioma
  • Proteoglycans
  • DNA
  • Transfection
Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Related Links

Latest Publications: BLYM (cancer-related)

Suspitsin EN, Yanus GA, Sokolenko AP, et al.
Development of breast tumors in CHEK2, NBN/NBS1 and BLM mutation carriers does not commonly involve somatic inactivation of the wild-type allele.
Med Oncol. 2014; 31(2):828 [PubMed] Related Publications
Somatic inactivation of the remaining allele is a characteristic feature of cancers arising in BRCA1 and BRCA2 mutation carriers, which determines their unprecedented sensitivity to some DNA-damaging agents. Data on tumor-specific status of the involved gene in novel varieties of hereditary breast cancer (BC) remain incomplete. We analyzed 32 tumors obtained from 30 patients with non-BRCA1/2 BC-associated germ-line mutations: 25 women were single mutation carriers (7 BLM, 15 CHEK2 and 3 NBN/NBS1) and 5 were double mutation carriers (2 BLM/BRCA1, 1 CHEK2/BLM, 1 CHEK2/BRCA1 and 1 NBN/BLM). Losses of heterozygosity affecting the wild-type allele were detected in none of the tumors from BLM mutation carriers, 3/18 (17 %) CHEK2-associated BC and 1/4 (25 %) NBN/NBS1-driven tumors. The remaining 28 BC were subjected to the sequence analysis of entire coding region of the involved gene; no somatic mutations were identified. We conclude that the tumor-specific loss of the wild-type allele is not characteristic for BC arising in CHEK2, NBN/NBS1 and BLM mutation carriers. Rarity of "second-hit" inactivation of the involved gene in CHEK2-, NBN/NBS1- and BLM-associated BC demonstrates their substantial biological difference from BRCA1/2-driven cancers and makes them poorly suitable for the clinical trials with cisplatin and PARP inhibitors.

Related: Breast Cancer CHEK2

Frenzilli G, Lori A, Panasiuk G, et al.
Comet assay on children's leukocytes 8 years after the Chernobyl disaster.
Mutat Res. 1998; 415(1-2):151-8 [PubMed] Related Publications
DNA damage, mainly single strand breaks, was evaluated by single cell gel electrophoresis, in leukocytes of 36 healthy and 14 thyroid cancer-affected children prior to radio-therapy. The children come from the Gomel region, one of the areas most heavily radio-contaminated by the Chernobyl fallout. In addition, leukocytes were treated with a challenge dose of bleomycin (BLM, 1.5 micrograms/ml), to assess the presence of an adaptive response (AR) potentially resulting from chronic exposure to radionuclides. As controls, 13 children living in Pisa (Italy) were enrolled in the study. Children with thyroid cancer show higher (p < 0.001) DNA damage than healthy ones. No difference was found between healthy children from Gomel and from Pisa. A reduction in the response to BLM was significantly linked to low plasma levels of FT4 hormone (p < 0.0001), to the presence of the tumor (p < 0.002), to being female (p < 0.02), and to a higher 137Cs body burden (p < 0.03).

Related: Bleomycin Thyroid Cancer

Kubota Y, Nakada T, Yanai H, et al.
Electropermeabilization in bladder cancer chemotherapy.
Cancer Chemother Pharmacol. 1996; 39(1-2):67-70 [PubMed] Related Publications
PURPOSE: Electropermeabilization has been used for the introduction of genes into cells. Using this technique, we introduced the cytotoxic drug bleomycin (BLM) into cells and examined whether the technique might be useful for the treatment of bladder cancer.
MATERIALS AND METHODS: For electropermeabilization in vitro, we used YTS-1 cells, a human transitional cell carcinoma line. Aliquots of cell suspension were mixed with a solution of BLM and immediately exposed to electric pulses. A high-power pulse generator was used to supply square-shaped pulses of 1250 V/cm (100 micros, eight pulses). After a 2-h post-shock incubation, cells were washed and incubated for one further hour. Then the concentration of BLM in the cells was measured using a bioassay. For electropermeabilization of tissue, we used normal male Wistar rats. The bladder was exposed and 10 mg/kg BLM was injected into the caudal vein. A series of eight pulses with a time constant of 100 micros at an electric field intensity of 1000 V/cm was applied. The bladder, liver and lungs were extracted 1 h later and prepared for quantification of the BLM concentration using the bioassay.
RESULTS: Electrotreated cells contained significantly higher concentrations of BLM than nonelectrotreated cells. The concentration of BLM 1 h after electrotreatment in bladder tissue was 2.7 times higher than that in nonelectrotreated bladder tissue.
CONCLUSION: The electropermeabilization technique has the potential to serve as a new and effective modality for the treatment of bladder cancer.

Related: Bleomycin Transitional Cell Cancer of the Renal Pelvis and Ureter Bladder Cancer Bladder Cancer - Molecular Biology

Yamanaka T, Hishinuma A
[Different effects of anticancer drugs on two human thyroid cell lines with different stages of differentiation].
Nihon Naibunpi Gakkai Zasshi. 1995; 71(1):73-86 [PubMed] Related Publications
We established two human thyroid tumor cell lines. One cell line (hPTC) was established from the tissue of a papillary thyroid carcinoma surgically excised from a 27-year-old female patient. The other cell line (hAG) was established from the tissue of an adenomatous goiter excised from a 59-year old female patient. Synthesis of cAMP by hPTC and hAG increased when they were stimulated by TSH. hPTC and hAG continued to divide as a monolayer in a tissue culture for three years and two years, respectively. We assessed the efficacy of anticancer drugs (doxorubicin:ADR, cisplatin:CDDP, nimustine:ACNU, bleomycin:BLM, cyclophosphamide:CPA, aclarubicin:ACR) with resard to hPTC. The hPTC cells were cultured in 24-well plates in the presence of the anticancer drugs for 48 hours, and the cellular DNA of the live cells was measured with diaminobenzoic acid. ADR had the lowest ED50 (0.029 mu g/ml) and the clinical blood concentration was 13.8 times that of the ED50. The clinical blood concentration divided by ED50 for the other anticancer drugs are, in order of higher values, 2.3 for CPA, 1.7 for BLM, 1.2 for CDDP, 0.5 for ACR, and less than 0.1 for ACNU. ADR showed time-independent effects since a 2-hour exposure of ADR to the hPTC cells resulted in the significant reduction of the cellular DNA content of the live cells even after 48 hours. The effects of the other anticancer drugs were time-dependent. We then studied the difference of the effects of ADR on hPTC and hAG. ED50 for hPTC was significantly low (0.035 mu g/ml) compared to that for hAG (0.460 mu g/ml). Since free radical formation is one of the major anticancer mechanisms of ADR the effects of free radicals on ED50's for hPTC and hAG were measured by adding glutathione (GSH), N-acetylcystein (NAC), buthionine sulfoximine (BSO), and alpha-tocopherol (alpha-toco) into the culture media. GSH catches up with free radicals in the extracellular fluid. NAC promotes production of GSH in the cytoplasm, but BSO interferes with the production of GSH in the cytoplasm. alpha-toco catches up with free radicals on the plasma membrane. GSH and alpha-toco did not effect ED50 for hPTC and hAG. However, NAC increased ED50 for hPTC and hAG, and BSO reduced ED50 for hPTC and hAG. The effects of NAC and BSO on ED50 for hPTC were greater than those for hAG.(ABSTRACT TRUNCATED AT 400 WORDS)

Related: Thyroid Cancer

Urade M, Ogura T, Uematsu T, et al.
Induction of bleomycin resistance in a human oral squamous carcinoma cell line and characterisation of bleomycin-resistant and -sensitive clones.
Eur J Cancer B Oral Oncol. 1994; 30B(6):409-14 [PubMed] Related Publications
We examined the change of sensitivity to antitumour agents by repeated treatment with bleomycin (BLM) using two oral squamous carcinoma cell lines, SCCTF and SCCKN. SCCTF exhibited minimal sensitivity to BLM and strong heterogeneity in BLM sensitivity, whereas SCCKN was highly sensitive to BLM and showed weak heterogeneity. When SCCTF was treated continuously with low-dose BLM (0.1 microgram/ml) but not intermittently with high-dose BLM (1 microgram/ml), the BLM sensitivity was rapidly decreased to acquire drug resistance. On the other hand, SCCKN was completely killed by the same treatments. To investigate the mechanism of induction of resistance in SCCTF, BLM-sensitive and -resistant clones, TF-S and TF-R, were isolated and analysed. Consequently, TF-R showed decreased cellular accumulation and retention of BLM, increased BLM hydrolase activity and elevated DNA repair activity concomitant with increased poly(ADP-ribose) polymerase activity as compared with TF-S. Therefore, it was suggested that antitumour drug-resistant clones were selectively grown from heterogeneous tumour cell population.

Related: Bleomycin

Zhu JD, Pan HO, Suzuki F, Takigawa M
Proto-oncogene expression in a human chondrosarcoma cell line: HCS-2/8.
Jpn J Cancer Res. 1994; 85(4):364-71 [PubMed] Related Publications
HCS-2/8 is a stable human chondrosarcoma cell line with many chondrocytic characteristics and has the capacity to form chondrosarcomas in nude mice. The cells display both biochemically and morphologically definable changes in sparse, subconfluent, confluent and over-confluent phases of in vitro culture. Such features of HCS-2/8 cells may reflect the processes of both proliferation and differentiation of chondrocytes in vivo. We examined the correlations of these changes of HCS-2/8 cells with their transcript levels of 21 proto-oncogenes by Northern analysis. We found no detectable transcripts of 9 proto-oncogenes (c-sis, c-met, c-src, c-lyn, c-fgr, c-ros, c-pim, Blym and N-myc), but detected transcripts of 12 other proto-oncogenes (int-2, erbB, c-abl, c-raf-1, c-fyn, K-ras, H-ras, c-mos, c-myc, c-myb, c-fos, and c-jun). In the over-confluent phase, the levels of c-fos and c-raf-1 were increased several dozen times and about 5 times, respectively, while the level of c-abl was about 1/5th of that in the sparse, subconfluent and confluent phases of culture. The level of int-2 increased about 10-fold in the confluent and over-confluent phases of in vitro culture. The transcript levels of c-mos and K-ras were high in the sparse phase, low in the subconfluent and confluent phases and high in the over-confluent phase. The levels of the other 6 proto-oncogenes in HCS-2/8 cells were constant in all phases of in vitro culture.

Related: Chondrosarcoma

Ishiguro N, Matsui T, Shinagawa M
Specific expression of cellular oncogenes c-myc and c-myb in T-cell lines established from three types of bovine lymphosarcomas.
Am J Vet Res. 1993; 54(12):2010-4 [PubMed] Related Publications
Expression of cellular oncogenes in 3 lymphoid cell lines, BTL-PC3 (BoCD2-, BoCD4-, BoCD8-, BoWC1+), BLS1 (BoCD2+, BoCD4-, BoCD8-, BoWC1+) and BLT2 (BoCD2-, BoCD4-, BoCD8-, BoWC1-), which have been established from calf, skin, and thymic types of lymphosarcomas, respectively, were analyzed by DNA-RNA (northern blot) hybridization. To determine specific expression of oncogenes involved in malignant transformation of the lymphoid cells, cellular RNA was isolated from bovine tumor cell lines, BTL-PC3, BLS1, and BLT2, and from Madin Darby bovine kidney cells used as a control for bovine cell lines. The RNA was hybridized against 5 viral oncogene probes (v-jun, v-myc, v-erbB, v-erbA and v-fes), 6 human cellular oncogene probes (N-ras, c-Blym-1 c-erbB-2, c-fos, c-myb and c-abl), human p53 tumor suppressor gene, and bovine LDH-A gene probes. Line BTL-PC3 expressed 2.4-kilobase (kb) c-myc and 4.0- and 3.6-kb c-myb transcripts, and line BLT2 expressed a 3.8-kb c-myb transcript, but line BLS1 expressed no message for the oncogenes tested. Specific transcripts of p53 were found in BTL-PC3 and BLT2 lines, but not in BLS1. Madin Darby bovine kidney cell line expressed multiple cellular oncogenes, c-jun, c-myc, and c-fos, and p53 genes. Southern blot hybridization did not reveal abnormal DNA rearrangements associated with the expressed oncogenes (c-myc and c-myb) in the 3 bovine tumor lines. (ABSTRACT TRUNCATED AT 250 WORDS)

Related: Non Hodgkin's Lymphoma Skin Cancer

Tanaka K, Sato C, Maeda Y, et al.
Establishment of a human malignant meningioma cell line with amplified c-myc oncogene.
Cancer. 1989; 64(11):2243-9 [PubMed] Related Publications
A new cell line (KT21-MG1) has been established from a human malignant meningioma transplanted into nude mice. The cultured cells showed epithelial cell-like morphology and were positive immunohistochemically for vimentin as the original tumor. They have been grown continuously in vitro for more than 2 years. The population doubling time was about 24 hours at the 30th passage. The cells are capable of proliferating in soft agar medium and produced tumors in nude mice, the histologies of which were similar to the original patient-derived tumor. Analysis of cellular oncogenes showed that myc and fps were amplified approximately tenfold and threefold, respectively, in this cell line, whereas N-myc, L-myc, N-ras, K-ras, H-ras, abl, erbB2, Blym, src, raf-1, myb, and sis were not changed significantly. The amplification of myc was accompanied by an enhanced expression. Chromosome studies of cultured cells showed the monosomy of chromosome 22 that has been reported to be a specific abnormality in meningiomas.

Savelyeva L, Mamaeva S
Population analysis of karyotypic heterogeneity of the Raji Burkitt lymphoma cell line. Analysis of 100 karyotypes.
Cancer Genet Cytogenet. 1988; 34(1):63-75 [PubMed] Related Publications
A constant lymphoblastoid line Raji (Burkitt lymphoma) has been used as a model for population cytogenetic studies. In analyzing 100 G-banded metaphase plates, four karyotypically distinct clones of cells with 48 chromosomes have been recognized, forming a modal class. In tracing the origin of marker chromosomes (in all 15), the presence of material specific for Burkitt chromosome markers 14q+ and 8q- has been shown. The application of the method of karyotype reconstruction has shown a uniformity in the overall chromosome material of all four groups of cells despite a different set of normal and marker chromosomes. The presence of 40% of cells with unique structural rearrangements (USR) demonstrated, to a significant extent, the structural instability of chromosomes in Raji cells. The nonrandom nature of distribution of "hot spots" along the chromosomes in the process of formation of both markers and USR has been shown. A preferential involvement of chromosomes #6, #7, and #8, as well as of separate regions 1p32, 6q15, 11q13, and 21p13 has been recorded. This report discusses aspects of karyotypic heterogeneity of cell populations in vitro and structural instability of regions of chromosomes #1 and #11, that coincide with the localization of the oncogene L-MYC or sequence BLYM-1 and the oncogene BCL-1.

Kudriavets IuI, Kiseleva NP, Asanova AA, Pinchuk VG
[Expression of oncogenes in transplantable tumors and rodent cell lines].
Biull Eksp Biol Med. 1988; 106(7):86-8 [PubMed] Related Publications
The expression of 8 oncogenes in transplanted rodent tumours and cell lines was tested. In 6 cases the synthesis of myc-, fos-, ras-oncogene RNA was observed. The transcription of these oncogenes was observed nonspecifically in tumours of different histological types. No difference in the set of the oncogenes expressed and the size of their transcripts was noticed between transplanted tumours and the cell lines obtained from them. The expression of myb-, sis-, Blym-, erb-B- and abl-was not observed in tested cells.

Popescu NC, Chahinian AP, DiPaolo JA
Nonrandom chromosome alterations in human malignant mesothelioma.
Cancer Res. 1988; 48(1):142-7 [PubMed] Related Publications
Malignant mesothelioma (MM) is a neoplasm closely associated with asbestos exposure, which has been implicated in 70-80% of the cases. In this study, nine MM (two fresh surgical specimens, two permanent cell lines, and five xenografts in nude mice) were examined cytogenetically. Six patients had a known history of asbestos exposure. Seven MM were chromosomally abnormal, the majority having complex structural alterations affecting different chromosomes, whereas two fresh surgical specimens had a normal chromosome constitution. Alterations of chromosome 3 were detected in seven cases and changes involving chromosomes 1 and 7 were observed in six cases. The breakpoints of translocations and deletions on chromosome 1 involved several bands; however, 50% of the breakpoints were near the locations of Blym, L-myc, and ski protooncogenes. Forty % of the breaks on chromosome 7 involved bands q11.1-11.2 and 20% were at q22, the location of the met protooncogene. Nonrandom changes on chromosome 3 were interstitial or terminal deletions, and translocations involving the region p14-21. The deleted 3p segment was identifiable as part of a chromosome translocation in one MM and was apparently lost in the other six. The deletions involving 3p are either spontaneous or asbestos-induced lesions at vulnerable genomic sites and are the most common and nonrandom chromosome alterations observed. Possibly 3p abnormalities are causally related to the development of this malignancy.

Related: Chromosome 1 Chromosome 3 Chromosome 7 Mesothelioma

Billings PC, Weichselbaum RR, Kennedy AR
Expression and methylation of the Blym gene in human tumor cell lines.
Eur J Cancer Clin Oncol. 1987; 23(3):331-7 [PubMed] Related Publications
We have examined Blym expression in 11 human tumor cell lines. Increased Blym expression was observed in one of three osteosarcoma cell lines relative to nontransformed human foreskin fibroblasts. In addition, enhanced Blym expression was observed in a melanoma cell line and in 2 of 6 squamous carcinoma cell lines relative to nontransformed, low passage human epithelial cells. We found no evidence of gene amplification or rearrangements of Blym sequences in any of the cell lines we have examined. We further analyzed the state of methylation of the Blym gene in several of the tumor cell lines by Msp I/Hpa 11 restriction endonuclease digestion. All cell lines examined had similar Msp I digestion patterns. However, the different tumor cell lines had different Hpa 11 digestion patterns. Therefore, our results indicate that the Blym gene is differentially expressed and methylated in human tumor cell lines.

Kessler DJ, Heilman CA, Cossman J, et al.
Transformation of Epstein-Barr virus immortalized human B-cells by chemical carcinogens.
Cancer Res. 1987; 47(2):527-31 [PubMed] Related Publications
Epstein-Barr virus-immortalized human lymphocytes were used to analyze the transition from the benign hyperproliferative to the malignant transformed state. Treatment with N-acetoxy-2-acetylaminofluorene, a potent frameshift mutagen, induced conversion of the Epstein-Barr virus immortalized lymphocytes into high-grade "immunoblastic lymphomas" on injection into athymic mice, whereas injection of the untreated, original cells did not. The tumor cells were all of the B-cell lineage as determined by the presence of surface immunoglobulins and antigens detected by B-cell specific antibodies to B1 and B4, and the absence of the T-cell-specific markers, 3A1 and LEU-1. The N-acetoxy-2-acetylaminofluorene-induced tumor lines displayed abnormal diploid to tetraploid karyotypes. The fewest chromosomal rearrangement, excluding tetraploidy, observed in these chemically induced lymphomas involved a deletion in chromosome 6, and additions on both chromosomes 16 and 4. Neither major rearrangements nor amplifications were found for K-ras, H-ras, N-ras, c-myc, Blym, and c-myb in these tumor lines.

Devine JM
Mechanism of activation of HuBlym-1 gene unresolved.
Nature. 1986 May 22-28; 321(6068):437-9 [PubMed] Related Publications
The HuBlym-1 gene has been isolated from Burkitt's lymphoma DNA on the basis of its reported ability to produce foci of cells when NIH 3T3 cells are transfected with it. The sequence of HuBlym-1 has been reported but it has not been established whether the sequence of the transforming gene differs from that of the gene in normal tissue, as might be expected from the common observation of mutational activation of proto-oncogenes into oncogenes. I report here that there are no differences between the sequences of three recombinant DNA clones that were isolated from Burkitt's cell lines and that cross-hybridize to HuBlym-1 but do not induce foci when transfected into NIH 3T3 cells, and the reported sequence of Burkitt's lymphoma Blym. Also there is no obvious or consistent increase in the transcription of the HuBlym-1 gene in Burkitt's lymphoma cell lines of the type that might otherwise have accounted for its transforming activity even in the absence of a mutation. How the HuBlym-1 gene is activated therefore remains a mystery.

Rowley PT, Kosciolek B, Bader JL
Oncogene expression in neurofibromatosis.
Ann N Y Acad Sci. 1986; 486:327-32 [PubMed] Related Publications
To investigate the role of oncogenes in malignancies characteristic of neurofibromatosis, oncogene transcripts were quantitated in a neurofibrosarcoma and in control tissue from a patient with hereditary neurofibromatosis. Sis and N-ras were moderately hyperexpressed, raf, Blym, and erbA were slightly hyperexpressed, and abl, erbB, fes/fps, fgr, fos, mos, myb, myc, N-myc, rasHarvey, rasKirsten, ros, src, and yes were not hyperexpressed in the tumor compared to the control tissue. Although additional tumors will be assayed before conclusions are possible, it may be significant that the two oncogenes most hyperexpressed are prior suspects for a pathogenetic role in tumors of the nervous system.

Related: Skin Cancer

Hu LF, Li XL, Jiang JQ, et al.
Transforming activity of human nasopharyngeal carcinoma DNA.
J Cell Physiol Suppl. 1986; 4:21-6 [PubMed] Related Publications
NIH 3T3 cells were transfected with the DNAs from biopsy specimens of human nasopharyngeal carcinoma (NPC, EBV DNA positive) using calcium phosphate precipitation method. The malignant, transformed foci of NIH 3T3 cells have been observed and cloned. The hybridization of transfectant DNA digested by EcoRI with total human leukocyte DNA as probe was performed. The strong signal of smear comparing with NIH 3T3 DNA as control was observed. It was implied that the putative human transforming sequences had been integrated into transformed cells. Employing soft agar culture, the transformed cells can grow and form cell colonies. Following transfer, the foci were able to grow and adhere to a glass wall. These cells were easily agglutinated by con A. The cloned foci have been inoculated into nude mice with the formation of highly malignant sarcomas. In preliminary experiments for characterizing the transforming sequences, Ha-ras and Blym 1 were found in transfectants derived from one of the NPC DNA samples. It is implicated that these two oncogenes might be responsible for the acquisition of malignant phenotypic character of some human NPC. The further identification of oncogenes in NPC is currently in progress.

Related: Nasopharyngeal Cancer

Hirai H, Tanaka S, Azuma M, et al.
Transforming genes in human leukemia cells.
Blood. 1985; 66(6):1371-8 [PubMed] Related Publications
High-molecular weight DNAs of fresh bone marrow cells from 32 patients with fresh leukemia were assayed for the presence of transmissible activated transforming genes by a DNA-mediated gene transfer technique using NIH/3T3 cells. DNAs of bone marrow cells from four of the 32 patients induced transformation of NIH/3T3 cells. Two of the four cases, a chronic myelogenous leukemia and an acute lymphocytic leukemia, contained activated N-ras oncogenes. Molecular cloning and nucleotide sequence analysis revealed that the lesion responsible for the transforming activity was localized to a single nucleotide transition from guanine to thymine in codon 12 of the predicted protein in each of the two cases. These observations indicate that activation of N-ras oncogenes is independent of the specific stage of cell differentiation or the leukemia phenotype. The other two transforming genes associated with an acute myelogenous leukemia and an acute lymphocytic leukemia showed homology neither with members of the ras gene family nor with the human Blym-1 gene. Thus, the NIH/3T3 transfection assay frequently detects activated N-ras oncogenes in human leukemias, while other transforming genes, distinct from the ras gene family, can be detected in some leukemias by the transfection assay.

Related: Leukemia

Diamond A, Devine JM, Lane MA, Cooper GM
The isolation and characterization of the Blym-1 transforming gene.
Basic Life Sci. 1985; 33:141-52 [PubMed] Related Publications
There are a number of similarities between chicken bursal lymphomas and human Burkitt's lymphomas. Both lymphomas are associated with viral infection, by LLV in bursal lymphomas and Epstein-Barr virus in Burkitt's lymphoma. Avian lymphoid leukosis virus integration is associated with enhanced c-myc expression, while the role EBV plays in tumorigenesis remains unclear. In Burkitt's lymphoma, however, c-myc activation does occur as a result of specific chromosomal translocations involving the human c-myc locus. Furthermore, the activated transforming genes detected by transfection of both bursal lymphoma and Burkitt's lymphoma DNAs are homologous members of the Blym family of genes. These similarities between chicken and human lymphomas provide evidence that viral involvement and oncogene activation are significant in tumor development and suggest they are involved in the multi-step progression to the neoplastic phenotype. The function of the Blym genes remains to be determined. Although the chicken and human Blym genes are only distantly related, they have maintained their homology to the amino-terminal regions of transferrins. This fact may reflect some functional constraint on the evolution of these genes. It is therefore possible that transforming genes such as Blym may function via a transferrin-related mechanism.

Neiman P, Wolf C, Enrietto PJ, Cooper GM
A retroviral myc gene induces preneoplastic transformation of lymphocytes in a bursal transplantation assay.
Proc Natl Acad Sci U S A. 1985; 82(1):222-6 [PubMed] Free Access to Full Article Related Publications
Treatment of chicken embryos with cyclophosphamide results in ablation of bursal lymphocytes. Bursal follicles can be reconstructed by infusion of embryonic bursal cells. Histologic examination of reconstituting bursal follicles showed that the first lymphocytes to appear were large pyrinophilic lymphoblasts that lined up adjacent to the bursal basement membrane and appeared to serve as progenitors for the differentiation of bursal medullary lymphocytes. When these cells were infected with the avian myelocytomatosis virus HB1 bearing a v-myc oncogene they appeared to home to the region of the bursal basement membrane but failed to differentiate. Instead, they formed structures indistinguishable from the preneoplastic transformed follicles that develop during bursal lymphomagenesis induced by lymphoid leukosis viruses. The DNA from these transformed follicles contained the HB1 v-myc gene but lacked the ability to transform NIH/3T3 mouse cells. Therefore these preneoplastic lesions were induced directly by HB1 myc and did not require the expression of Blym-1 or similar oncogenes. Exploitation of this transplantation technique with the chicken bursa will provide a useful method for assessing the stage-specific activity of oncogenes in vivo.

Neiman P
The Blym oncogenes.
Adv Cancer Res. 1985; 45:107-23 [PubMed] Related Publications

Cooper GM
Structure and function of ras and Blym oncogenes.
Haematol Blood Transfus. 1985; 29:273-6 [PubMed] Related Publications

Glazer PM, Summers WC
Oncogene expression in isogenic, EBV-positive and -negative Burkitt lymphoma cell lines.
Intervirology. 1985; 23(2):82-9 [PubMed] Related Publications
To elucidate the mode of action of Epstein-Barr virus (EBV), we have examined the possibility that EBV infection may lead to a change in oncogene expression. Levels of oncogene-related RNA were compared in the Burkitt lymphoma(BL)-derived, EBV-negative cell line BJAB and in two isogenic, EBV-converted sublines of BJAB whose growth characteristics differ from the EBV-negative parent line. The oncogenes c-myc, Ha-ras, and Blym were each found to be expressed at equally high levels in the three cell lines. This suggests that the mechanism of action of EBV in altering the growth properties of lymphoid cells is not dependent on the induction of cellular oncogenes. In addition, since the 8,14 chromosomal translocation has been related to increased c-myc expression in BL cells, a karyotype analysis was done to confirm the initial report of a normal karyotype in BJAB cells. Chromosomes 8 and 14 were seen to be normal. Thus, BJAB cells are a BL cell line in which the elevated expression of c-myc is independent not only of EBV but also of translocations involving chromosome 8.

Diamond A, Devine JM, Cooper GM
Nucleotide sequence of a human Blym transforming gene activated in a Burkitt's lymphoma.
Science. 1984; 225(4661):516-9 [PubMed] Related Publications
The nucleotide sequence of a human Blym-1 transforming gene activated in a Burkitt's lymphoma cell line was determined. This sequence predicts a small protein of 58 amino acids that is 33 percent identical to the predicted product of chicken Blym-1, the activated transforming gene of chicken B cell lymphomas. Both the human and chicken Blym-1 genes exhibit significant identity to an amino-terminal region of transferrins.

Clarke MF, Westin E, Schmidt D, et al.
Transformation of NIH 3T3 cells by a human c-sis cDNA clone.
Nature. 1984 Mar 29-Apr 4; 308(5958):464-7 [PubMed] Related Publications
The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. It is unusual among haemopoietic cell lines in that one of these is c-sis, the gene from which the oncogene v-sis of the simian sarcoma virus was derived, and perhaps the gene for platelet-derived growth factor (PDGF). To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. This is the first example of transformation of NIH-3T3 cells by a human onc gene other than c-ras or Blym, as well as the first demonstration of transformation by a human cDNA clone.

Related: Leukemia

Morton CC, Taub R, Diamond A, et al.
Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1.
Science. 1984; 223(4632):173-5 [PubMed] Related Publications
Blym-1, a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymphomas, was mapped to the short arm of chromosome 1 (1p32) by chromosomal in situ hybridization. The Blym-1 gene was not physically linked to the cellular myc oncogene or to any of the immunoglobulin gene loci implicated in the characteristic chromosomal translocations in Burkitt lymphoma.

Devine JM, Diamond A, Lane MA, Cooper GM
Characterization of the Blym-1 transforming genes of chicken and human B-cell lymphomas.
J Cell Physiol Suppl. 1984; 3:193-8 [PubMed] Related Publications

Cooper GM
Structural and functional analysis of ras and Blym oncogenes.
Curr Top Microbiol Immunol. 1984; 113:34-6 [PubMed] Related Publications

Habs M, Schmähl D
Carcinogenicity of bleomycin sulfate and peplomycin sulfate after repeated subcutaneous application to rats.
Oncology. 1984; 41(2):114-9 [PubMed] Related Publications
Bleomycins (BLM) are widely used as antineoplastic agents either alone or in combination regimens. Results of earlier studies in experimental animals were said to be inadequate to evaluate the carcinogenicity of BLM, which is a known mutagen. In a dose-response study, BLM and peplomycin (PEP) were investigated in Sprague-Dawley rats of both sexes. For the first 10 weeks weekly doses of 0.35, 0.70, 1.40, and 2.80 mg/kg BLM and of 0.32, 0.63, 1.25, 2.50, and 5.0 mg/kg PEP were applied subcutaneously (BLM: 30 male and 30 female rats/group; PEP: 25 male and 25 female rats/group). In the case of BLM, thereafter the doses were given once every fortnight either for 1 year (BLM: 1.40 and 2.80) or for life (lower doses). In the case of PEP, application of the high doses was stopped after the 13th time (5.0: 10 X 1/week and 3 X 1 every 2 weeks) and the 19th application (2.5 mg: 10 X 1/week and 9 X 1/every 2 weeks). After the 10th dosing, the remaining groups were treated once every fortnight for life. 60 male and 60 female rats served as solvent-treated (physiological saline) controls. The animals were observed for life. Repeated doses of BLM and PEP reduced body weight and life expectancy of the animals in a dose-related pattern. Tubular cell damages and cell proliferations were seen as a symptom of major toxicity in the kidneys. In this model BLM and PEP are carcinogenic: treatments resulted in significant dose-related incidences of animals with tumors at the site of application (fibrosarcomas) and with renal tumors (adenomas, adenocarcinomas, sarcomas).

Related: Bleomycin Kidney Cancer Skin Cancer

Diamond A, Cooper GM, Ritz J, Lane MA
Identification and molecular cloning of the human Blym transforming gene activated in Burkitt's lymphomas.
Nature. 1983 Sep 8-14; 305(5930):112-6 [PubMed] Related Publications
DNAs of six Burkitt's lymphoma cell lines contained an activated transforming gene detected by transfection of NIH 3T3 cells. This gene was cloned from a recombinant library of Burkitt's lymphoma DNA and identified as a human homologue of chicken Blym-1, the transforming gene detected by transfection of chicken B-cell lymphoma DNA.

Suzuki M, Nomura H, Ito M, et al.
[Therapy of cancer of the female genitalia with a new antineoplastic drug, bleomycin (BLM). 1. Basic study of bleomycin].
Sanfujinka No Jissai. 1969; 18(4):375-9 [PubMed] Related Publications


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