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PubMed2026

Genomic and functional characterization of sugar transporters reveals potential roles in sugar accumulation in a modern sugarcane cultivar.

Sugarcane (Saccharum spp.) is a globally important sugar crop whose productivity depends on efficient sugar transport from source to sink organs. However, systematic identification and functional characterization of sugar transporters (STs) in sugarcane cultivars remain limited. Here, we identified 190 non-redundant ST genes in sugarcane cultivar Guitang 42 (GT42) and phylogenetically classified them into nine groups within the Monosaccharide Transporter (MST), Sucrose Transporter (SUT), and Sugars Will Eventually be Exported Transporters (SWEET) families. Comparative evolutionary analysis revealed significant lineage-specific expansions in the PMT, STP subfamilies, and SWEET families compared to diploid and wild relatives, likely driven by polyploidization and intensive selection for sugar yield. Transcriptomic profiling across tissues and internode elongation stages demonstrated marked tissue-specific and developmental expression patterns. Yeast complementation assays confirmed the transport activity of candidate MSTs, SUTs and SWEETs, with confocal microscopy verifying their distinct subcellular localization at the plasma membrane, tonoplast, or endoplasmic reticulum. Furthermore, transient overexpression of several candidate transporters (ScSWEET4-T2, ScSWEET15, and ScTST4-T1) in Nicotiana benthamiana modulated soluble sugar accumulation, and their expression in sugarcane protoplasts activated key sugar-responsive marker genes (ScGPT2 and ScWIP4). Together, our study establishes a systematic genomic framework and identifies candidate functional transporters that govern sugar partitioning and storage, providing valuable genetic targets for molecular breeding and quality enhancement in sugarcane.

Functional characterization↗
PubMed1987

Structure of the human oestrogen-responsive gene pS2.

The human pS2 gene, whose expression is restricted to breast cancer cells, and whose transcription is induced by oestrogen in the human breast cancer cell line MCF-7, has been cloned from both placental and MCF-7 cell DNA. The exon-intron organization has been established by electron microscopy using genomic DNA-cDNA or -mRNA hybrid duplexes and by sequencing the exons and exon-intron junctions. The overall organization within and around the pS2 gene is the same in placental and MCF-7 cell DNA and the exonic sequences are identical to those previously determined from the cDNA. The 5'-flanking region of the pS2 gene is also identical (with the exception of two base transitions) in the two tissues. Thus no gene rearrangement nor sequence modification has occurred in the pS2 gene of the malignant and polyploid MCF-7 cells. A TATA-box, a CAAT-box and a GC-rich motif are present in the 5'-flanking region of the pS2 gene, but the latter motif is unusually located between the TATA-box and the capsite. No significant homology could be detected between the 5' flanking sequences of the pS2 gene and those of other oestrogen-responsive genes from different species.

Amino Acid Sequence↗
PubMed2006

Catching a 'hopeful monster': shepherd's purse (Capsella bursa-pastoris) as a model system to study the evolution of flower development.

Capsella is a small genus within the mustard family (Brassicaceae). Its three species, however, show many evolutionary trends also observed in other Brassicaceae (including Arabidopsis) and far beyond, including transitions from a diploid, self-incompatible, obligatory outcrossing species with comparatively large and attractive flowers but a restricted distribution to a polyploid, self-compatible, predominantly selfing, invasive species with floral reductions. All these evolutionary transitions may have contributed to the fact that Capsella bursa-pastoris (shepherd's purse) has become one of the most widely distributed flowering plants on our planet. In addition, Capsella bursa-pastoris shows a phenomenon that, although rare, could be of great evolutionary importance, specifically the occurrence of a homeotic variety found in relatively stable populations in the wild. Several lines of evidence suggest that homeotic changes played a considerable role in floral evolution, but how floral homeotic varieties are established in natural populations has remained a highly controversial topic among evolutionary biologists. Due to its close relationship with the model plant Arabidopsis thaliana, numerous experimental tools are available for studying the genus Capsella, and further tools are currently being developed. Hence, Capsella provides great opportunities to investigate the evolution of flower development from molecular developmental genetics to field ecology and biogeography, and from morphological refinements to major structural transitions.

Biological Evolution↗
PubMed2005

Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis.

BACKGROUND AND AIMS: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. METHODS: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. RESULTS: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis (low activity: 75.1 (18.8)% v high activity: 61.8 (21.6)%, p=0.0111, and low fibrosis: 77.3 (13.8)% v high fibrosis: 57.4 (23.3)%, p=0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis (low activity: 11.9 (15.5)% v high activity: 22.2 (20.1)%, p=0.0166, and low fibrosis: 9.4 (10.7)% v high fibrosis: 26.4 (21.6)%, p=0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections (HBV: 18.2 (7.6)% v HCV: 12.0 (4.8)%; p=0.0020). Under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction (p=0.0294). CONCLUSION: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.

Adult↗
PubMed2026

Transposable elements as modulators of homoeologous gene expression in bread wheat: lessons from the pan-transcriptome era.

Bread wheat (Triticum aestivum L.) is an allohexaploid (AABBDD) whose three ancestral subgenomes generate complex patterns of gene regulation. Most genes exist as homoeologous triads, and the relative expression balance among copies, homoeolog expression bias, is central to polyploid evolution and adaptation. Recent high-quality assemblies, long-read transcriptomics, and pan-transcriptome resources have uncovered extensive cultivar-specific transcriptional diversity. Because transposable elements (TEs) compose over 80% of the wheat genome, they are prime candidates for shaping subgenome asymmetry. We synthesize recent pan-genomic and transcriptomic evidence, including genome-wide associations between TE insertions and genome-specific expression, and propose a unifying framework in which TEs modulate homoeolog expression by donating cis-regulatory sequences, altering chromatin states, producing small RNAs, and driving structural variation. We discuss experimental and computational challenges for establishing causality, and outline future functional and translational strategies to leverage TE-associated regulatory diversity in wheat breeding.

Triticum↗
PubMed2006

Mechanisms of genomic rearrangements and gene expression changes in plant polyploids.

Polyploidy is produced by multiplication of a single genome (autopolyploid) or combination of two or more divergent genomes (allopolyploid). The available data obtained from the study of synthetic (newly created or human-made) plant allopolyploids have documented dynamic and stochastic changes in genomic organization and gene expression, including sequence elimination, inter-chromosomal exchanges, cytosine methylation, gene repression, novel activation, genetic dominance, subfunctionalization and transposon activation. The underlying mechanisms for these alterations are poorly understood. To promote a better understanding of genomic and gene expression changes in polyploidy, we briefly review origins and forms of polyploidy and summarize what has been learned from genome-wide gene expression analyses in newly synthesized auto-and allopolyploids. We show transcriptome divergence between the progenitors and in the newly formed allopolyploids. We propose models for transcriptional regulation, chromatin modification and RNA-mediated pathways in establishing locus-specific expression of orthologous and homoeologous genes during allopolyploid formation and evolution.

Chromosomes, Plant↗
PubMed2026

Contrasting regulation of protein-coding genes and lncRNA homeologs in allotetraploid Coffea arabica.

A chromosome-level Bourbon assembly revealed that protein-coding homeologs are predominantly co-regulated between subgenomes. In contrast, intergenic lncRNAs display a modest, but statistically consistent bias toward subgenome E across diverse developmental and stress contexts. Coffea arabica is an allotetraploid species derived from natural hybridization between C. canephora and C. eugenioides, which contributed the C and E subgenomes, respectively. This genomic origin poses major challenges for genome assembly, annotation, and the interpretation of gene regulation. In this study, a high-quality genome assembly of C. arabica was generated and annotated, with particular emphasis on identifying protein-coding genes and intergenic long non-coding RNAs (lincRNAs). Homeologous relationships between genes from the C and E subgenomes were established, providing a robust framework to investigate subgenomic conservation and regulatory divergence. Using an extensive collection of publicly available RNA-seq libraries spanning multiple developmental stages, tissues, and environmental conditions, the relative transcriptional contribution of each subgenome was evaluated. On a global scale, gene expression was largely balanced between subgenomes, with no consistent evidence of subgenome dominance. While protein-coding genes showed comparable regulatory behavior across subgenomes, lincRNAs exhibited a more asymmetric expression pattern, suggesting higher subgenome-specific expression that is interpreted here as a consistent directional tendency rather than as evidence of subgenome dominance. Together, these results provide new insights into the regulatory architecture of the C. arabica genome and establish a foundational genomic and transcriptomic resource for future functional studies and crop improvement efforts.

Coffea↗
PubMed2003

Metal-catalyzed oxidation of extracellular matrix components perturbs hepatocyte survival with activation of intracellular signaling pathways.

To investigate whether oxidative manipulation of extracellular matrix components could affect cell survival, we studied primary rat hepatocytes cultured on dishes coated with collagen type 1, which was oxidized with a metal-based system. Culture of hepatocytes on oxidized collagen led to decreased cellular catalase activity along with impaired cell survival. The fraction of polyploid hepatocytes decreased early followed by greater reaccumulation of polyploid cells. Cells cultured on oxidized collagen showed greater susceptibility to additional oxidant stress induced by tert.-butyl-hydroperoxide. The capacity of hepatocytes for growth factor-induced DNA synthesis was unaffected by culture on oxidized collagen. In response to culture on oxidized matrix, AP-1, Egr-1, CREB, and NF-kappaB transcription factor activity was rapidly increased. This change in transcription factor activity was ameliorated by treatment of collagen with a free radical spin trap, N-tert.-butyl-alpha-phenylnitrone, prior to oxidation. Moreover, culture of hepatocytes with aminoguanidine, an antioxidant drug, decreased cell injury. These findings established that exposure of primary hepatocytes to oxidized extracellular matrix components rapidly activates cell signaling events with loss of hepatocyte subpopulations. Such cell-extracellular matrix interactions may play roles in organ homeostasis and oncogenetic progression.

Animals↗
PubMed2026

Periplasmic SacB as a robust counter-selection tool for genome engineering in the polyploid bacterium Zymomonas mobilis.

UNLABELLED: The alpha-proteobacterium Zymomonas mobilis exhibits exceptional ethanologenic physiology, which makes it a traditional alcoholic beverage producer and a promising chassis for biofuel production. Although genetic tools for this organism have expanded in recent years, a fundamental aspect of its chromosome organization remains to be understood. In particular, Z. mobilis has been suggested to exhibit polyploidy, but this feature is not fully confirmed because of discrepancies among studies reporting the copy number of chromosomes. Here, we tagged the chromosome-partitioning protein ParB with a fluorescent marker to visualize its cellular localization and estimate chromosome copy number in individual cells. Imaging showed that Z. mobilis exhibits several distinctive ParB foci throughout the cytoplasm and an accumulated focus at the pole, indicating that a single Z. mobilis cell contains >5 copies of the chromosome at the oriC regions. We then sought to establish an efficient counter-selection system, which is crucial for engineering multiple copies of the chromosome. We assessed the efficacy of levan-sucrase (SacB) toxicity in Z. mobilis. We found that, despite Z. mobilis secreting a native extracellular sucrase SacB, heterologous periplasmically localized Bacillus subtilis SacB rendered Z. mobilis cells sensitive to sucrose. We successfully used this effect for counter-selection when deleting and inserting targeted DNA sequences into the Z. mobilis genome. Together, this work provides important insights and tools for advancing Z. mobilis genetics and its biotechnological applications. IMPORTANCE: Zymomonas mobilis is a promising industrial bacterium with the capacity to convert sugars into ethanol at nearly maximum theoretical yield. With its expanding use in industrial applications, it is crucial to clarify if individual Z. mobilis cells carry multiple copies of the chromosome, as this has important implications for genome engineering. Two previous studies have used quantitative PCR to address this question, but their reported chromosome copy numbers varied widely from 20 to 100. Here, we used a cell biological approach to estimate the copy number and confirmed that a single Z. mobilis cell possesses multiple copies. In addition, we show that a SacB-based counter-selection works in Z. mobilis, enabling efficient and complete mutation of all chromosome copies.

Zymomonas↗
PubMed1995

Determination of chromosome copy numbers in Saccharomyces cerevisiae strains via integrative probe and blot hybridization techniques.

Methods have been devised for analyzing chromosome copy numbers in S. cerevisiae strains that may be polyploid or aneuploid, as is apparent in the case of many industrial strains. The initial step involved transformation of a strain with an integrative "ploidy probe" transplacement fragment that enabled the copy number of the targeted chromosomal locus to be determined via genomic Southern blotting and quantitative probe hybridization. Dual probe co-hybridization to Southern genomic DNA blots was used to extend such locus copy number determinations to other loci within the same chromosome, thereby screening for internal consistency along the length of the chromosome. This approach was also used to extend the analysis to other chromosomes in the genome. The method was established and verified with euploid series laboratory strains and then used to examine chromosome copy numbers in three industrial strains. One brewing strain apparently contained three copies of the chromosomes tested, whilst another brewing and a baking strain showed evidence of aneuploidy.

Blotting, Southern↗
PubMed1998

Establishment and characterization of a human glioblastoma multiforme cell line.

Cell lines provide a useful system for further understanding the biology of glioblastoma multiforme. In this study, a new glioblastoma multiforme cell line, GATAGM-96 (Gulhane Askeri Tip Akademisi-Gliblastoma Multiforme-96), was established from a tumor specimen removed from an 80-year-old male patient who underwent surgery for intracranial tumor. Morphologic examination, immunocytochemical staining, growth kinetics, and karyotypic characteristics of this cell line were studied. The cytoskeleton was positive for neuron-specific enolase, vimentin, and neurofilament, and it was negative for glial fibrillary acidic protein, S-100 protein, p53 protein, epidermal growth factor, and transforming growth factor alpha. Growth kinetic studies demonstrated an approximate population doubling time of 38 to 42 h and a colony forming efficiency of 83.3%. The karyotype of the cells demonstrated it as hyperdiploid, with a large subpopulation of polyploid cells. There were numerous structural and numerical chromosome aberrations; most of them were present as clonal events. The phenotypic and chromosomal features detailed on the GATAGM-96 cell line should make it a useful addition to the cell lines currently available for in vitro and in vivo studies of glioblastoma multiforme.

Aged↗
PubMed2000

[Genome multiplication in the trophoblasts and glandular epithelium of endometrium during embryo implantation and placentation of silver fox].

Dynamics of genome multiplication during establishment of interrelations between the trophoblast and the glandular epithelium of endometrium was studied in the course of placenta formation in the silver fox. Endometrium response on the embryo implantation exhibits some features of inflammation. In the course of placenta formation the trophoblast gains access to the endometrial glandular epithelium zone, while the endometrial blood vessels grow the other way into the expanding trophoblast zone. The trophoblast gradually replaces the whole epithelium and part of the stroma of the endometrium, closely adjoining the endometrial vessels but not disrupting them. Cytophometric DNA measurements in the trophoblast nuclei have shown that most of the nuclei are polyploid: predominantly 4c-64c, occasionally 128c and 256c. Polyploidy of the trophoblast may result from various types of polyploidizing mitoses. Cytophotometric DNA measurements in mitotic figures have revealed mitoses with DNA amounts equal to 4c (2n), 8c (4n), and 16c (8n), which indicates that trophoblast cells in the silver fox placenta are able to enter mitosis prior to the octaploid level. Higher degrees of polyploidy in the trophoblast cells may be achieved presumably by endoreduplication. In the silver fox polyploidization of uterine grandular epithelial cells during placentation occurs until the level of 8c. Thus, the tissue-specific response of the uterus to the implanting embryo is an active proliferation and polyploidization of the glandular epithelium, rather than formation of a population of polyploid decidual cells (i.e. connective tissue cells). Using the silver fox endotheliochorial placenta as an example, a regularity has been confirmed that cells of both maternal and fetal origin are polyploid in sites of their contact in placenta, which might be of protective significance in the contact of allogenic organisms.

Animals↗
PubMed2002

Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling.

Fibrinogen binding to integrin alphaIIbbeta3 mediates platelet aggregation and requires agonist-induced "inside-out" signals that increase alphaIIbbeta3 affinity. Agonist regulation of alphaIIbbeta3 also takes place in megakaryocytes, the bone marrow cells from which platelets are derived. To facilitate mechanistic studies of inside-out signaling, we describe here the generation of megakaryocytes in quantity from murine embryonic stem (ES) cells. Coculture of ES cells for 8-12 days with OP9 stromal cells in the presence of thrombopoietin, IL-6, and IL-11 resulted in the development of large, polyploid megakaryocytes that produced proplatelets. These cells expressed alphaIIbbeta3 and platelet glycoprotein Ibalpha but were devoid of hematopoietic stem cell, erythrocyte, and leukocyte markers. Mature megakaryocytes, but not megakaryocyte progenitors, specifically bound fibrinogen by way of alphaIIbbeta3 in response to platelet agonists. Retrovirus-mediated expression of the reporter gene, green fluorescent protein, in ES cell-derived megakaryocytes did not affect viability or alphaIIbbeta3 function. On the other hand, retroviral expression of CalDAG-GEFI, a Rap1 exchange factor identified by megakaryocyte gene profiling as a candidate integrin regulator, enhanced agonist-induced activation of Rap1b and fibrinogen binding to alphaIIbbeta3 (P < 0.01). These results establish that ES cells are a ready source of mature megakaryocytes for integrin studies and other biological applications, and they implicate CalDAG-GEFI in inside-out signaling to alphaIIbbeta3.

Animals↗
PubMed2002

Pollen competition as a unilateral reproductive barrier between sympatric diploid and tetraploid Chamerion angustifolium.

Speciation requires the evolution of barriers to gene exchange between descendant and progenitor populations. Cryptic reproductive barriers in plants arise after pollination but before fertilization as a result of pollen competition and interactions between male gametophytes and female reproductive tissues. We tested for such gametic isolation between the polyploid Chamerion angustifolium and its diploid progenitor by conducting single (diploid or tetraploid) and mixed ploidy (1 : 1 diploid and tetraploid) pollinations on both cytotypes and inferring siring success from paternity analysis and pollen-tube counts. In mixed pollinations, polyploids sired most (79%) of their own seeds as well as those of diploids (61%) (correcting for triploid block, siring success was 70% and 83%, respectively). In single donor pollinations, pollen tubes from tetraploids were more numerous than those from diploids at four different positions in each style and for both diploid and tetraploid pollen recipients. The lack of a pollen donor x recipient interaction indicates that the tetraploid siring advantage is a result of pollen competition rather than pollen-pistil interactions. Such unilateral pollen precedence results in an asymmetrical pattern of isolation, with tetraploids experiencing less gene flow than diploids. It also enhances tetraploid establishment in sympatric populations, by maximizing tetraploid success and simultaneously diminishing that of diploids through the production of inviable triploid offspring.

Crosses, Genetic↗
PubMed1990

Prognostic significance of DNA-ploidy in a series of 690 primary breast cancer patients.

Flow cytometric DNA-ploidy measurements were performed on paraffin-embedded and fresh tumor specimens from 690 patients with Stage I-III breast cancer. The conventional classification of DNA-ploidy (diploid versus aneuploid) was compared with a division of tumor ploidy into 5 classes based on DNA index (DI) range. The DI-classification showed a better correlation with tumor size and TNM stage than the conventional classification. Aneuploidy was associated with an impaired survival and distant relapse-free survival (p = 0.02) but the DI-classification improved the discrimination between different prognostic groups of patients. In general, this indicated a more aggressive phenotype for tumors evolved via polyploidization. Hyper-tetraploidy (DI greater than 2.10) indicated a very poor prognosis in pre-menopausal patients. No prognostic effect of aneuploidy and DI-class was found in node-negative and TI patients. Cox multivariate regression analysis showed that aneuploidy was an additional prognostic factor to nodal status (I less than or equal to N less than or equal to 3, N greater than 3 vs. N = 0) and tumor size (T2-4 vs. TI) for overall and distant relapse-free survival. Subdivision according to DI-class did not improve the prognostic power of DNA-ploidy due to stronger correlations with established prognostic factors.

Aged↗
PubMed1987

High NaCl induces stable changes in phenotype and karyotype of renal cells in culture.

Extracellular fluid in the renal medulla normally is hyperosmotic. To test adaptation to such an environment, a continuous line of rabbit renal inner medullary epithelial cells (GRB-PAP1), which had been established in isosmotic medium, was switched to a medium containing high NaCl. The origin of these cells is described. When the osmolality was raised from 300 to 600 mosmol/kg by adding NaCl, cells eventually survived and proliferated, but unexpectedly, they underwent major changes in phenotype and karyotype that persisted during proliferation in isosmotic or hyperosmotic medium for at least 7 months. The threshold concentration for the changes was approximately 500 mosmol/kg. Cells of a typical strain (PAP-HT25) that formed in hyperosmotic medium were much larger and more often multinucleated than were GRB-PAP1. GRB-PAP1 cells were near diploid; PAP-HT25 cells were polyploid. The changes, since they occurred in most clones, were due to adaptation of the majority of cells and not to selection of a minority of cells already having these characteristics. Cloning efficiency was higher for GRB-PAP1 than PAP-HT25 in isosmotic medium, but the reverse occurred in hyperosmotic medium. Thus exposure to the hyperosmotic medium induced greater ability to clone in it. We suggest that these changes may involve persistent alterations in gene regulation, possibly like those previously reported in chicken embryo fibroblast cells after hyperosmotic NaCl (Cell 30: 131-139, 1982).

Animals↗
PubMed1987

Chromosomal progression of malignant human gliomas from biopsy to establishment as permanent lines in vitro.

Karyotypes of four malignant human gliomas were followed from direct preparation and/or short-term culture through their establishment in vitro to determine whether the cultured cells maintained the original karyotypes, or were the products of selection, progression, or alteration in vitro. The karyotypes of these four human glioma-derived cell lines showed the same evolutionary pattern consisting of a doubling of the stem line or a closely related population; one line changed ploidy again to near-pentaploid. Marker types seen originally were generally retained, but new markers were acquired in the later passages. We concluded that the eventual chromosomal compositions of these four human glioma-derived cell lines were the products of karyotypic evolution, rather than simple selection of a minor population of polyploid cells.

Cell Line↗
PubMed2005

A notable phenomenon recapitulated. A fusion product of a murine lymphoma cell and a leukemia virus-neutralizing antibody-producer host plasma cell formed spontaneously and secreting the specific antibody continuously.

In the mid-1960s the #620 cell passage line of a murine lymphoma-leukemia was developed at the Section of Clinical Tumor Virology and Immunology, Department of Medicine, The University of Texas M.D. Anderson Hospital in Houston, TX. The diploid lymphoma cells released a retrovirus and were antigenic in young adult Swiss (YAS) mice. Small lymphoma cell inocula were rejected with immunity acquired against large inocula of lymphoma cells. Tissue sections revealed the "starry sky" configurations. In one of the tissue cultures set up from lymphoma #620, a cell line consisting of large round poly- or tetraploid cells arose and was referred to as lymphoma cell line #818. The #818 cells grew in suspension cultures and in the form of large, lethal ascitic tumors in YAS mice. Diploid #620 lymphoma cells stained for retroviral antigens; #818 cells stained both for retroviral antigens and immunoglobulins. Fluids withdrawn from #818 cultures neutralized the leukemia virus in spleen focus assays. Immunoglobulin precipitated from #818 suspension culture fluids strongly and specifically neutralized the leukemia virus. The growth of #620 or #818 cells in YAS mice treated with rabbit anti-lymphoma cell immune sera was strongly inhibited but culture fluids of #818 cells showed weak and insignificant inhibition against leukemia-lymphoma #620 (in one experiment, unpublished). In two experiments #620 lymphoma cells were co-inoculated with immune spleen cells into the peritoneal cavities of YAS mice. The immune spleen cells derived from mice that rejected #620 cell inocula or were actively immunized with a photodynamically inactivated mouse leukemia virus vaccine. In the peritoneal cavities of mice co-inoculated with #620 cells and immune spleen cells, clones of large round cells emerged with tetra- or polyploid chromosomal modes. These cells stained for leukemia viral antigens and immunoglobulins. When passaged in YAS mice these cells induced lethal ascites tumors. It was concluded as early as in 1968-69 that an immune plasma cell can fuse with a lymphoma cell, if the lymphoma cell expresses retroviral antigens against which the plasma cell is producing a specific antibody. Some human lymphoma-leukemia cells express retroviral antigens and/or budding retroviral particles, whether due to the acquisition of new env sequences by incomplete resident endogenous retroviral genomes or due to the entry of exogenous retroviruses into lymphopoietic stem cells. In the Discussion illustrations are provided for the human cell line #778 established from a patient with "lymphosarcoma cell leukemia" in 1966. The malignant cells released unidentified retrovirus-like particles and fused with one another and with reactive lymphoid cells of the host. It should be investigated further if human lymphoma-leukemia cells could fuse with an immune plasma cell of the host and thus alter the clinical course of the disease.

Animals↗