Summary
Recent studies on the molecular biology of the lymphocyte of chronic lymphocytic leukemia confirm the neoplastic nature of these cells. Functional and structural differences in the biochemistry of DNA, RNA and proteins define the biological peculiarity of this disease in which oncorna viruses are probably of no pathogenetic importance. Cells of chronic lymphocytic leukemia are characterized by various macromolecular abnormalities: multiple DNA-polymerases after PHA-stimulation, decreased actinomycin binding capacity, altered transcription of the chromatin, elevated DNA-repair, increased RNA-synthesis, increased synthesis of ribosomal precursors combined with a failure in ribosomal maturation, different32P nucleotide composition and oligonucleotide frequencies of nuclear 45S RNA and ribosomal 28S RNA, impairment in stimulation of nucleolar “processing” by PHA, decreased lysosome and polysome content, functional impairment of ribosomes in cell-free systems, new hybridizable polyribonucleotide sequences in nuclear heterogeneous RNA as well as qualitative and quantitative differences in the nuclear proteins after two-dimensional mapping by gel electrophoresis. The interpretation of the CLL-lymphocyte as a B-like cell does not seem to be sufficient with respect to the new biochemical data.
Zusammenfassung
Die jüngsten molekularbiologischen Untersuchungen an Lymphocyten der chronisch-lymphatischen Leukämie bestätigen den neoplastischen Charakter dieser Zellen. Funktionelle und strukturelle, z.T. qualitative Unterschiede in der Biochemie von DNA, RNA und Proteinen belegen die biologischen Sonderstellung dieser Erkrankung, bei deren Pathogenese Oncornaviren nach den bisher gesicherten Befunden wahrscheinlich keine Bedeutung haben. Zellen der chronisch-lymphatischen Leukämie sind durch verschiedenste makromolekulare Abnormalitäten ausgezeichnet: multiple DNA-Polymerasen nach PHA-Stimulation, vermindertes Aktinomycin-Bindungsvermögen, veränderte Transcription des Chromatins, erhöhten DNA-repair, erhöhte RNA-Synthese, vermehrte Synthese ribosomaler Vorstufen bei mangelhafter Ribosomenreifung, veränderte32P-Nucleotidkomposition und veränderte Oligonucleotidfrequenzen in nuclearer 45S RNA und ribosomaler 28S RNA, mangelhafte Stimulierung des nucleolaren „processing“ durch PHA, verminderten Lysosomen- und Polysomengehalt, Funktionseinbuße der Ribosomen in zellfreien Systemen, neue Polyribonucleotidsequenzen in der nuclearen heterogenen RNA sowie durch qualitative und quantitative Veränderungen des Kernproteinmusters nach zweidimensionaler Gel-Elektrophorese. Die Interpretation des CLL-Lymphocyten als Bähnliche Zelle erscheint im Zusammenhang mit diesen neuen biochemischen Daten als nicht ausreichend.
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Literatur
Aisenberg, A.C., Bloch, K.J., Long, J.C., Colvin, R.B.: Reaction of normal human lymphocytes and chronic lymphocytic leukemia cells with an antithymocyte antiserum. Blood41, 417 (1973)
Allfrey, V.G., Faulkner, R., Mirsky, A.E.: Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. nat. Acad. Sci. (Wash.)51, 786 (1964)
Ambs, E., Gronemeyer, R.: Die Nucleolenmorphologie von Lymphocyten des peripheren Blutes. Acta haemat. (Basel)48, 104 (1972)
Anday, G.J., Goodman, J.R., Tishkoff, G.H.: An unusual cytoplasmic ribosomal structure in pathologic lymphocytes. Blood41, 439 (1973)
Attardi, G., Amaldi, F.: Structure and synthesis of ribosomal RNA. Ann. Rev. Biochem.39, 183 (1970)
Augenlicht, L.H., Baserga, R.: Preparation and partial fractionation of nonhistone chromosomal proteins from human diploid fibroblasts. Arch. Biochem. Biophys.158, 89 (1973)
Begemann, H., Rastetter, H., Fink, U.: Zur Klassifizierung der Lymphocyten. Med. Klin.58, 706 (1963)
Benninghoff, D. L., Girardet, R. E., Porteous, D. D.: Thoracic duct and blood lymphocytes in cancer. Lancet1973 II, 264
Bernard, C., Geraldes, A., Boiron, M.: Effects of phytohemagglutinin on blood cultures of chronic lymphocytic leukemia. Lancet1964 I, 667
Bernard, W., Leplus, R.: Fine structure of normal and malignant human lymph node. Oxford: Pergamon Press 1964
Braunsteiner, H., Fellinger, K., Pakesch, F.: Electron microscope investigation on sections from lymph nodes and bone marrow in malignant blood diseases. Blood12, 278 (1957)
Bremer, K.: Kinetics of autotransfused lymphocytes in normal and in leukemic and non-leukemic lymphoma patients. Increased fraction of non-migrating lymphocytes in untreated chronic lymphocytic leukemia. Second Meeting of the European and African Division of the International Society of Hematology, Prague Abstracts vol. 2, p. 382 (1973)
Britten, R.J., Kohne, D.E.: Repeated sequences in DNA. Science161, 529 (1968)
Busch, H., Smetana, K.: The Nucleolus. New York: Academic Press 1970
Chiarugi, V.P.: Changes in nuclear RNA in hepatomas as revealed by DNA/RNA hybridization. Biochim. biophys. Acta (Amst.)179, 129 (1969)
Church, R.B., Luther, S.W., McCarthy, B.J.: RNA synthesis in Taper hepatoma and mouse liver cells. Biochim. biophys. Acta (Amst.)190, 30 (1969)
Clausen, K.P., Bouroncle, B.A.: The ultrastructure of phytohemagglutinin (PHA) stimulated lymphocytes of chronic lymphocytic leukemia. Blood34, 179 (1969)
Clayton, D.A., Smith, C.A., Jordan, J.M., Teplitz, M., Vinograd, J.: Occurrence of complex mitochondrial DNA in normal tissues. Nature (Lond.)220, 976 (1968)
Clayton, D.A., Vinograd, J.: Circular dimer and catenate forms of mitochondrial DNA in human leukemic leucocytes. Nature (Lond.)216, 652 (1967).
Cohnen, G., Douglas, S.D., König, E., Brittinger, G.: Pokeweed mitogen response of lymphocytes in chronic lymphocytic leukemia: A fine structural study. Blood42, 591 (1973)
Cooper, H.L.: Lymphocyte RNA-labelling with3H-uridine: correction of data by analysis of UTP pool saturation kinetics. Proceedings of the Seventh Leucocyte Culture Conference, p. 119. New York: Academic Press 1973
Cooper, H.L.: Ribonucleic acid metabolism in lymphocytes stimulated by phytohemagglutinin. II. Rapidly synthesized ribonucleic acid and the production of ribosomal ribonucleic acid. J. biol. Chem.243, 34 (1968)
Cooper, H.L.: Ribosomal ribonucleic acid production and growth regulation in human lymphocytes. J. biol. Chem.244, 1946 (1969)
Dameshek, W.: Chronic lymphocytic leukemia—an accumulative disease of immunologically incompetent lymphocytes. Blood29, 566 (1967)
Douglas, S.D., Cohnen, G., König, E., Brittinger, G.: Lymphocyte lysosomes and lysosomal enzymes in chronic lymphocytic leukemia. Blood41, 511 (1973)
Dupuy-Coin, A.M., Bouteille, M.: Developmental pathway of granular and beaded nuclear bodies from nucleoli. J. Ultrastruct. Res.40, 55 (1972)
Emerson, C.P.: Control of rRNA production in non-growing cells. Nature (Lond.) New Biol.236, 32 (1972)
Evans, R.G., Norman, A.: Radiation stimulated incorporation of thymidine into the DNA of human lymphocytes. Nature (Lond.)217, 455 (1968)
Frey-Wettstein, M., Longmire, R., Craddock, C.G.: Deoxyribonucleic acid repair replication of ultraviolet irradiated normal and leukemic leukocytes. J. Lab. clin. Med.74, 109 (1969)
Goldstein, L., Ron, A.: On the possibility of nuclear protein involvement in the control of DNA synthesis in amoeba proteus. Exp. Cell Res.55, 144 (1969)
Goldstein, L., Prescott, D.M.: Proteins in nucleocytoplasmic interaction. I. The fundamental characteristics of the rapidly migrating proteins and the slow turnover proteins of the amoeba proteus nucleus. J. Cell Biol.33, 638 (1967)
Grey, H.M., Rabellino, E., Prifosky, B.: Immunglobulins on the surface of human lymphocytes. IV. J. clin. Invest.50, 2368 (1971)
Grundmann, E.: Der morphologische Nachweis von zwei Lymphocytensystemen beim Menschen. Klin. Wschr.37, 941 (1959)
Hausen, P., Stein, H.: On the synthesis of RNA in lymphocytes stimulated by phytohemagglutinin. I. Europ. J. Biochem.4, 401 (1968)
Helinski, D.R., Clewell, D.B.: Circular DNA. In: E.E. Snell (ed.), Ann. Rev. Biochem., vol. 40, p. 899. Palo Alto, Cal.: Annual Reviews, Inc. 1971
Henry, P., Reich, P., Karon, M., Weissman, S.M.: Characteristics of RNA synthesized in vitro by lymphocytes of chronic lymphocytic leukemia. J. Lab. clin. Med.69, 47 (1967)
Higashi, K., Matsuhisa, T., Gotoh, S., Nishinaga, K., Sakamoto, Y.: Different gene expression for ribosomal RNA of AH-130 tumor and embryonic and adult rat liver. Biochim. biophys. Acta (Amst.)232, 352 (1971)
Higashi, K., Gotoh, S., Nishinaga, K., Sakamoto, Y.: Further evidence of heterogeneity of ribosomal RNA in various rat tissues. Biochim. biophys. Acta (Amst.)262, 320 (1972)
Huang, A.T., Kremer, W.B., Laszlo, J., Setlow, R.B.: DNA repair in human leukaemic lymphocytes. Nature (Lond.) New Biol.240, 114 (1972)
Hyman, G.A., Fingerhut, B., Tiburcio, A.C.: Possible defect in RNA metabolism in leukaemic cells. Cancer (Philad.)21, 357 (1968)
Kay, J.E., Handmaker, S.D.: Uridine incorporation and RNA synthesis during stimulation of lymphocytes by PHA. Exp. Cell Res.63, 411 (1970)
Kellermayer, M., Lehane, D.E., Lane, M., Freireich, E.J., Busch, H.: Two-dimensional polyacrylamide gel electrophoretic analysis of leukemic and normal human lymphocyte nuclear proteins. (In Vorbereitung.)
Klein, E., Eskeland, T., Inoue, M., Strom, R., Johansson, B.: Surface immunoglobulin-moieties on lymphoid cells. Exp. Cell Res.62, 133 (1970)
Laszlo, J., Huang, A.T.F., Cremer, W.B.: Studies on human leukemic cells and normal lymphocytes. In: H. Busch, K. Smetana (eds.), Methods in cancer research, vol. V., p. 373. New York: Academic Press 1970
Levine, A.S., Oxman, M.N., Eliot, H.M., Henry, P.H.: New species of rapidly hybridizing RNA of contactinhibited as well as transformed hamster cell lines. Cancer Res.32, 506 (1972)
Lichtman, M.A., Weed, R.I.: Electrophoretic mobility and N-acetyl neuraminic acid content of human, normal and leukaemic lymphocytes and granulocytes. Blood35, 12 (1970)
Lille, I., Desplaces, A., Meeus, L., Saracino, R.T., Brouet, J.C.: Thymus-derived proliferating lymphocytes in chronic lymphocytic leukemia. Lancet1973 II, 263
Loeb, L.A., Poiesz, B.J., Williams, R.O., Springgate, C.: On multiple DNA-polymerase after stimulation of normal and leukaemic lymphocytes. Proceedings of the Seventh Leucocyte Culture Conference, p. 151. New York: Academic Press 1973
Masera, P., Pileri, A., Brachet, J., Hulin, N.: Lymphocyte actinomycin binding capacity in chronic lymphocytic leukemia. Experientia (Basel)28, 1484 (1972)
McLelland, D.A., Bridges, J.M.: The total N-acetylneuraminic acid content of human normal and lymphatic leukemic lymphocytes. Brit. J. Cancer27, 114 (1973)
Mertelsmann, R., Garbrecht, M., Heller-Schöch, G., Schöch, G.: DNA-dependent DNA and RNA polymerase activities in normal and leukaemic leucocytes: Characteristics and purification. 2nd Meeting of the European and African Division of the International Society of Hematology, Prague Abstracts vol. 1, p. 168 (1973)
Metzgar, R.S., Mohanakumar, T., Miller, D.S.: Antigens specific for human lymphocytic or myelogenous leukemia. Proc. Amer. Ass. Cancer Res.14, 49, Abstr. 193 (1973)
Mukherjee, A.B., Waite, R.G., Cohen, M.M., Bernstein, R.: Incorporation of uridine-3H and sodium acetate-14C in lymphocytes derived from normal and leukemic individuals. Cancer Res.32, 1833 (1972)
Muramatsu, M., Higashinakagawa, T., Ono, T., Sugano, H.: The nuclear RNA of minimal deviation hepatomas. Cancer Res.28, 1126 (1968)
Nass, M.M.K.: Mitochondrial DNA: Advances, problems and goals. Science165, 25 (1969)
Neiman, P.E., Henry, P.H.: Ribonucleic acid-deoxyribonucleic acid hybridization and hybridization-competition studies of the rapidly labelled ribonucleic acid from normal and chronic lymphocytic leukemia lymphocytes. Biochemistry8, 275 (1968)
Neiman, P.E., Henry, P.H.: DNA: RNA hybridization and competition studies of the newly synthesized radioactive ribonucleic acid from normal small lymphocytes and the lymphocyte of chronic lymphocytic leukemia. Blood30, 887 (1967)
Oppenheim, J.J., Whang, J., Frei, E., III: Immunologic and cytogenetic studies of chronic lymphocytic leukemia cells. Blood26, 121 (1965)
Orrick, L.R., Olson, M.O.J., Busch, H.: Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Proc. nat. Acad. Sci. (Wash.)70, 1316 (1973)
Papamichail, M., Brown, J.C., Holborow, E.J.: Immunoglobulins on the surface of human lymphocytes. Lancet1971 II, 850
Pernis, B.: In: Progress in immunology (Amos, D.B. Landy, M., eds.). New York: Academic Press 1972
Pernis, B., Ferrarini, M., Forni, L.: Immunoglobulin on lymphocyte membranes. In: Progress in immunology (Amos, B., ed.). New York: Academic Press 1971, p. 95
Pileri, A., Masera, P., Hulin, N., Brachet, J.: Actinomycin binding capacity in human leukaemic lymphoid cells. Acta haemat. (Basel)48, 89 (1972)
Pogo, B.G.T., Allfrey, V.G., Mirsky, A.E.: RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc. nat. Acad. Sci. (Wash.)55, 805 (1966)
Pogo, B.G.T., Allfrey, V.G., Mirsky, A.E.: The effect of phytohemagglutinin on ribonucleic acid synthesis and histone acetylation in equine leucocytes. J. Cell Biol.35, 477 (1967)
Polgar, P., Vera, J.C., Kelley, P.R., Rutenburg, A.M.: Adenylate cyclase activity in normal and leukemic human leucocytes as determined by a radioimmunoassay for cyclic AMP. Biochim. biophys. Acta (Amst.)297, 378 (1973)
Quagliarotti, G., Hidvegi, E., Wikman, J., Busch, H.: Structural analysis of nucleolar precursors of ribosomal ribonucleic acid. Comparative hybridizations of nuclear and ribosomal ribonucleic acid with nucleolar deoxyribonucleic acid. J. biol. Chem.245, 1962 (1970)
Ramsey, R.L., Ultmann, J.E.: Protein synthesis by ribosomes from blood lymphocytes of normals and patients with chronic lymphocytic leukemia. Proc. Soc. exp. Biol. (N.Y.)141, 839 (1972)
Rubin, A.D., Havemann, K., Dameshek, W.: Studies in chronic lymphocytic leukemia. Further studies of the proliferative abnormality of the blood lymphocyte. Blood33, 313 (1968)
Rubin, A.D.: Defective control of ribosomal RNA processing in stimulated leukemic lymphocytes. J. clin. Invest.50, 2485 (1971)
Rubin, A.D.: Possible control of lymphocyte growth at the level of ribosome assembly. Nature (Lond.)220. 196 (1968)
Sandberg, A.A., Hossfeld, D.K.: Chromosomal changes in human tumors and leukemias. Handbuch der allgemeinen Pathologio VI/5–6, Geschwülste (E. Grundmann, ed.). Berlin-Heidelberg-New York: Springer, im Druck 1974
Saunders, G.F., Shirakawa, S., Saunders, P.P., Arrighi, F.E., Hsu, T.C.: Populations of repeated DNA sequences in the human genome. J. molec. Biol.63, 323 (1972)
Sawada, H., Gilmore, V.H., Saunders, G.F.: Transcription from chromatins of human lymphocytic leukemia cells and normal lymphocytes. Cancer Res.33, 428 (1973)
Scherrer, K., Darnell, J.E.: Sedimentation characteristics of rapidly labeled RNA from HeLa cells. Biochim. biophys. Res. Commun.7, 486 (1962)
Schooley, J.C., Bryant, B.J., Kelly, L.S.: Preliminary autoradiographic observations of cellular proliferation in lymphoid tissues using triated thymidine. In: F. Stohlman (ed.). The kinetics of cellular proliferation. New York: Grune and Stratton 1959
Schrek, R.: The effect of phytohemagglutinin on lymphocytes from patients with chronic lymphocytic leukemia. Arch. Path.83, 58 (1967)
Schrek, R.: Ultrastructure of blood lymphocytes from chronic lymphocytic and lymphosarcoma cell leukemia. J. nat. Cancer Inst.48, 51 (1972)
Schumacher, H.R., Maugel, T.K., Davis, K.D.: The lymphocyte of chronic lymphatic leukemia. I. Electron microscopy-onset. Cancer (Philad.)26, 895 (1970)
Scott, J.L., McMillan, R., Marino, J., Davidson, J.G.: Leucocyte labelling with51Chromium. IV. The kinetics of chronic lymphocytic leukemia lymphocytes. Blood41, 155 (1973)
Seeber, S., Hertenstein, Ch., Schmidt, C.G.: Differences in nuclear RNA labelling patterns of Burkitt lymphoma, leukaemic lymphosarcoma and various human leukaemias. Klin. Wschr.51, 680 (1973)
Seeber, S., Schmidt, C.G.: Basenanalysen, Oligonucleotidfrequenzen und Markierungskinetik hochmolekularer Nucleinsäuren in menschlichen Lymphomen und Leukosen. Verh. dtsch. Ges. inn. Med. (1974) (im Druck)
Seeber, S.: Fehlerhafte Synthese ribosomaler Nucleinsäuren in menschlichen Leukämiezellen. Z. Krebsforsch.82, 159–173 (1974)
Seeber, S., Schmidt, C.G.: Isolation of rapidly labelled nuclear RNA of high specific activity from human leukaemic cells. Klin. Wschr.51, 677 (1973)
Seeber, S., Schmidt, C. G.: Isolation and characterisation of highly labelled ribosomal RNA from human leukaemic cells. Excerpta med. (Amst.) im Druck (1974)
Seeber, S., Brucksch, K.P., Käding, J., Schmidt, C.G., Busch, H.: Oligonucleotides of ribosomal 28S RNA in human leukemic cells and normal lymphocytes. Cancer Res.34, 1281–1288 (1974)
Seeber, S., Käding, J., Brucksch, K.P., Schmidt, C.G.: Defective ribosomal RNA synthesis in human leukaemic blast cells? Nature (Lond.)248, 673 (1974)
Seeber, S., Schmidt, C.G.: New parameters for a characterization of human leukemias. Second Meeting of the European and African Division of the International Society of Hematology, Prag. Abstracts vol 1, p. 171 (1973)
Seeber, S., Busch, H.: Comparative oligonucleotide sequences of ribosomal 28S RNA of normal liver and Novikoff hepatoma ascites cells. Cancer Res.31, 1888 (1971)
Seeber, S., Busch, H.: Structural analysis of nucleolar precursors of ribosomal ribonucleic acids. II. Polypurine sequences as chemical markers of processing of nucleolar 45S RNA. J. biol. Chem.246, 7151 (1971)
Shiguera, H.T., Chargaff, E.: Studies on the dynamics of ribonucleic acid formation. J. biol. Chem.233, 197 (1958)
Silber, R., Unger, K.W., Grooms, R.: RNA synthesis in normal leucocytes, leukemia and macroglobulinemia. Nature (Lond.)205, 1211 (1965)
Sitz, T.O., Nazar, R.N., Spohn, W.H., Busch, H.: Similarity of ribosomal and ribosomal precursor RNAs from rat liver and the Novikoff hepatoma. Cancer Res.,33, 3312 (1973)
Smetana, K., in Vorbereitung (1974)
Smetana, K., Gyorkey, F., Gyorkey, P., Busch, H.: Comparative studies on the ultrastructure of nucleoli in human lymphosarcoma cells and leukemic lymphocytes. Cancer Res.30, 1149 (1970)
Smetana, K., Gyorkey, F., Gyorkey, P., Busch, H.: Compact filamentous bodies of nuclei and nucleoli of human prostate gland. Exp. Cell Res.64, 133 (1971)
Smetana, K.: Electron microscopy of lymphocytes. In: Methods in cancer research (H. Busch, ed.), vol. 5, p. 455. New York: Academic Press 1970
Smetana, K., Freireich, E., Busch, H.: Chromatin structures in ring-shaped nucleoli of human lymphocytes. Exp. Cell Res.52, 112 (1968)
Smetana, K.: A further contribution to the question of the incidence of nucleoli in the lymphocyte of men. Folia biol. (Praha)7, 268 (1971)
Smetana, K., Lejnar, J., Potmesil, M.: A further contribution to the demonstration of RNA and nucleoli of blood cells in smear preparations. Folia haemat.91, 381 (1969)
Smetana, K.: Persönliche Mitteilung.
Smith, C.A., Vinograd, J.: Complex mitochondrial DNA in human tumours. Cancer Res.33, 1065 (1973)
Sokal, J.E., Lopez-Sandoval, R.: In vitro leucocyte thymidine uptake in chronic lymphocytic leukemia. Proc. Amer. Ass. Cancer Res.14, 41, 161 (1973)
Springgate, C.F., Loeb, L.A.: Mutagenic DNA polymerase in human leukaemic cells. Proc. nat. Acad. Sci. (Wash.)70, 245 (1973)
Stacher, A.: Zur Morphologie der Blutlymphocyten nach Pyrogen und ACTH. Wien. Z. inn. Med.44, 110 (1963)
Steele, W.J., Okamura, N., Busch, H.: Effects of thioacetamide on the composition and biosynthesis of nuclear and nucleolar RNA. J. biol. Chem.240, 1742 (1965)
Theml, H., Trepel, F., Schick, P., Kaboth, W., Begemann, H.: Kinetics of lymphocytes in chronic lymphocytic leukemia: Studies using continuous3H-thymidine infusion in two patients. Blood42, 623 (1973)
Theml, H., Trepel, F., Rastetter, J., Begemann, H.: DNS-und RNS-Synthese in benignen und malignen Lymphomen. Klin. Wschr.45, 609 (1967)
Thomas, J.A., Henry, M., Hollande, E.: Les corps intranucleaires des histiocytes alveolaires du lapin in vivo et in vitro: corps fibrilaires et corps nucleolaires. C.R. Acad. Sci. (Paris)275, 851 (1972)
Torelli, U.L., Torelli, G.M., Andreoli, A., Mauri, C.: Partial failure of methylation and cleavage of 45S RNA in the blast cells of acute leukemia. Nature (Lond.)226, 1163 (1970)
Torelli, U.L., Torelli, G.M., Andreoli, A., Mauri, C.: Impaired processing of ribosomal precursor RNA in blast cells of acute leukemia. Acta haemat. (Basel)45, 201 (1971)
Torelli, U.L., Torelli, G.M., Mauri, C.: Competition hybridization studies on rapidly sedimenting RNA of acute leukemia blast cells. Europ. J. Cancer8, 653 (1972)
Tryfiates, G.P., Laszlo, J.: Human leukaemic polyribosomes. Proc. Soc. exp. Biol. (N.Y.)124, 1125 (1967)
Tsai, M.J., Sawada, H., Gilmore, V.H., Saunders, G.F.: Transcription of chromatin by the DNA-dependent RNA polymerases of human leukemic leukocytes and E. coli. Fed. Proc.31, 428 (1972)
Turkington, R.W., Self, D.: New species of hybrididizable nuclear RNA in breast cancer cells. Cancer Res.30, 1833 (1970)
Turkington, R.W.: Changes in hybridizable nuclear RNA during the neoplastic development of mouse mammary cells. Cancer Res.31, 427 (1971)
Walker, P.M.B., McLaren, A.: Fractionation of mouse deoxyribonucleic acid on hydroxyapatite. Nature (Lond.)208, 1175 (1965)
Weisenthal, L.M., Ruddon, R.W.: Characterization of human leukemia and Burkitt lymphoma cells by their acidic nuclear protein profiles. Cancer Res.32, 1009 (1972)
Weissman, S.M., Henry, P., Karon, M., Wynngate, A.: Synthesis of acid-soluble proteins by the lymphocytes of chronic lymphocytic leukemia. J. Lab. clin. Med.67, 757 (1966)
Wikman, J., Howard, E., Busch, H.: Studies on the primary structure of ribosomal 28S RNA and its nucleolar precursors. Isolation of an electrophoretically homogeneous fragment rich in guanylic and cytidylic acids. J. biol. Chem.244, 5471 (1969)
Wilmanns, W., Neef, V.: Die Thymidylat-Synthetase in weißen Blutzellen und im Knochenmark unter normalen und pathologischen Bedingungen. Klin. Wschr.49, 755 (1971)
Wilms, K., Jaenicke, L.: Desoxyribonucleinsäure-Polymerase in menschlichen Leukocyten. Enzymaktivität bei Leukämien und Virusinfektionen. Klin. Wschr.46, 407 (1968)
Wilson, J.D., Nossal, G.J.V.: Identification of human T and B lymphocytes in normal peripheral blood and chronic lymphocytic leukemia. Lancet1971 II, 788
Wilson, J.D., Hurdle, A.D.F.: Surface immunoglobulins on lymphocytes in chronic lymphocytic leukaemia and lymphosarcoma. Brit. J. Haemat.24, 563 (1973)
Wulff, U.C., Desai, L.S., Foley, G.E.: Human leukaemic cells. Fractionation and characterization of ribonucleic acids. Exp. Cell Res.75, 39 (1972)
Wybran, J., Chantler, S., Fudenberg, H.H.: Isolation of normal T cells in chronic lymphatic leukaemia. Lancet1973 I, 126
Yeoman, L.C., Taylor, C.W., Busch, H.: Two-dimensional polyacrylamide gel electrophoresis of acid extractable nuclear proteins of normal rat liver and Novikoff hepatoma ascites cells. Biochem. biophys. Res. Commun.51, 956 (1973)
Yeoman, L.C., Taylor, C.W., Jordan, J.J., Busch, H.: Two-dimensional polyacrylamide gel electrophoresis of chromatin proteins of normal rat liver and Novikoff hepatoma ascites cells. Biochem. biophys. Res. Commun.53, 1067 (1973)
Yeoman, H., Seeber, S., Taylor, W.C., Busch, H.: In Vorbereitung
Zucker-Franklin, D.: Virus-like particles in the lymphocytes of a patient with chronic lymphocytic leukemia. Blood21, 509 (1963)
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Seeber, S., Schmidt, C.G. Makromolekulare Besonderheiten des Lymphocyten der chronisch-lymphatischen Leukämie (CLL). Klin Wochenschr 52, 1093–1102 (1974). https://doi.org/10.1007/BF01468619
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DOI: https://doi.org/10.1007/BF01468619