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CPM 5 C3Hif Aga 2 o 5pL .20pL AKR/J AKR/J C3H(f 2 6 2 Vi rus PeLLet 4.---------------, ~~--------------.~ TNC non-TNC CaUs Fig. 4. Biosynthesis of reverse transcriptase in short term cultures of AKR TNC and small thymus cell populations. TNC and single thymocyte fractions of 2-month-old C3H/f and AKR/J and of preleukemic 6-month-old AKR/J mice were cultured for 4 days. Culture supernatants were harvested repeatedly and sedimentable material ("virus pellet") was assayed for reverse transcriptase activity (Novak et al. 1979) observations on AKR thymocyte properties make such speculations quite attractive. Weissman et al. found that few normal but a high proportion of preneoplastic and neoplastic thymocytes express receptors for retroviruses (McGrath and Weissman 1979). As has been suggested for Epstein-Barr viruses in the case of human B lymphocytes (Schwarz 1980), binding of viruses to thymic T cells in AKR thymuses is thought to trigger proliferation (McGrath and Weissman 1979). Accepting this possibility, does the AKR abnormality reside in an atypical thymocyte response pattern, and does recognition ofTNCmembraneexpressed viral products lead to excessive mitotic activity? Irrespective of whether this proliferation is sufficient for subsequent transformation or whether it "only" provides some of the requirements for cancerogenic cytogenetic changes to occur (Klein 1979), we believe that the study of AKR TNC components will offer an approach to reinvestigate the role of lympho-epithelial interactions, which has been a matter of debate (Haas et al. 1977; Peled and Haran-Ghera 1978; Waksal et al. 1976). Acknowledgments We thank Mrs. Maria Döll for her excellent technical assistence and Mrs. Rosemary Schneider for typing this manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft. possible, though not yet proven, that a property of the thymocytes is the basis for the changes. AKR TNCs contain enormous numbers of thymocytes, which are, as their "normal" counterparts, morphologically intact and actively proliferate within the TNCs (Wekerle and Ketelsen 1980). AKR intra-TNC thymocytes, however, often show a very loose contact between their surface membranes and the surrounding epithelial caveolar membranes. At present it is not possible to decide whether the abnormal cell numbers are due to an enhanced intra-TNC proliferation or to an increased recruitment of immigrating thymocytes. Are the changes of AKR TNCs related to neoplastic thymocyte conversion? Lacking functional data, any consideration of this problem must be highly speculative. Yet, some References Arnesen K (1958) Preleukemic and early leukemic changes in the thymus of mice. Acta Pathol Microbiol Scand [A] 43:350-364 - DeHarven E (1964) Virus particles in the thymus of conventional and germfree mice. J Exp Med 120: 857-868 - Haas M, Sher T, Smolinsky S (1977) Leukemogenesis in vitro induced by thymus epithelial reticulum cells transmitting murine leukemia viruses. Cancer Res 37: 1800-1807 - Klein G (1979) Lymphoma development in mice and humans: Diversity of initiation is followed by convergent cytogenetic evolution. Proc Natl Acad Sei USA: 2442-2446 - Koppenheffer TL, Philips JH, Vankin GL (1978) C-type virus-Iymphocyte interactions in the developing mouse thymus. Am J Anat 153: 165-170 - Lerner RA, Wilson CB, DelVillano CB, McConahey PJ, Dixon FJ (1977) Endogeneous oncoviral expression in adult and fetal mice: Quantitative, histologie and physiologie studies of the major viral glyeoprotein 375
pg70. J Exp Med 143: 151-166 - McGrath MS, Weissman IL (1978) A receptor-mediated model of viralleukemogenesis: Hypothesis and experiments. In: Clarkson B, Marks PA, TillJE (eds) Differentiation of normal and neoplastic hematopoietic cells. Cold Spring Harbor Laboratory, New York, pp 577-589 - McGrath MS, Weissman IL (1979), AKR leukemogenesis: Identification and biological significance of thymic lymphoma receptors for AKR retroviruses. Cell 17:65-75 - Metcalf D (1966) Histologic and transplantation studies on preleukemic thymus of the AKR mouse. J Natl Cancer lost 37:425-442 - Novak U, Friedrich R, Mölling K (1979) Elongation of DNA complementary to 5' and of the avian sarcoma virus genome by the virion associated RNA dependent DNA polymerase. J Virol 30:438-452 - Peled A, Haran-Ghera N (1978) Lack of transformation of murine thymocytes by thymic epithelium. Nature 274:266-269 - Schwarz RS (1980) Epstein-Barr virus-oncogen or mitogen? (editorial). N Engl J Med 302: 1307-1308 - Siegier R, Rich MA (1963) Unilateral histogenesis of AKR thymic lymphoma. Cancer Res 23:1774-1781 - Waksal SD, Smolinsky S, Cohen IR, Feldman M (1976) Transformation of thymocytes by thymus epithelium derived from AKR mice. Nature 263:512-514 - Wekerle H, Ketelsen U-P (1980) Thymic nurse cells - la-bearing epithelium involved in T-Iymphocyte differentiation? Nature 283:402-404 - Wekerle H, Ketelsen U-P, Ernst M (1980) Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: Morphological and serological characterization. J Exp Med 151 : 925-944 376
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Haematology and Blood Transfusion 2
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Dr. Rolf Neth, Universitäts-Kinder
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Participants of the Meeting Aaronso
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Kurth, R, Friedrich-Miescher-Labora
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Wilsede Scholarship Holders (Grante
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Preface Gut ist eine Lehrart, wo ma
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Personal and scientific discussion
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Acknowledgement We should like to t
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Wilsede, June 21 1978 Memorial Trib
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limiting benign lymphoproliferative
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this most unlikely, however (for re
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longer subject to the same control
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Bregula U, Wiener F, Harris H (1971
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fresh lymph node biopsies from ten
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Fig. 3. Binucleate mitosis in an ob
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y Fig. 4. Schematic diagram of post
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than that among patients with Stage
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Tests of binding affinity, agglutin
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N Engl J Med 297: 963-968 - Green I
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Clinical Aspects
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"ring chromosome". "Mar" is marker,
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191 chromosomally abnormal patients
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tumors of both African and non-Afri
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Haematology and Blood Transfusion V
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Retrospective group 26/93 evolved l
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Treatment
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advantage in terms of duration of f
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leukaemia. An analysis of 168 patie
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11. Treatment Program Chemotherapy
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efractory congestive heart failure
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period (Sequence II) was gene rally
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children with a multiple drug proto
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DAYS 1 5 10 15 20 25 30 35 , I I I
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Biologically Drug Outcome fit" sens
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may counterbalance the potential be
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Ht (0--0) 50 40 30 20 10 0 Platelet
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10 7 ,-----------------------------
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11. Haematological and Biochemical
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0\ 0\ INTERFERON ... 10 3 rl E "'
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("pre-B" phenotype) has been descri
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human bone marrow cells exhibit the
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10 9.,0 MBKCC .. .,4 B prot:oool 1'
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demann W, Büehner T, Arlin Z, Gee
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-...l 00 a-tLDRENS CAt«:ER S TU>Y
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prognostic characteristics under in
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significantly higher in HR} (14.5%,
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normal or elevated immunoglobulin l
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References Andreeff M, Darzynkiewic
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R GROUP 1 ( 1970 - 1971 ) 17 PTS. R
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Table 3. Influence of initial featu
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LIJ (f) a.. < -1 LIJ Q: u. 0 >- I-
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me nt indicated that additional the
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42:2123-2134 - Chessells JM, Cornbl
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Baum et al. 1979). This study was b
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1. 0 '--'1--" 0.9 e: o .- VI VI E C
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e: o e: 1. 0 ,.--...-- 1'"'\ ......
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In conclusion, we can state that th
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Haematology and Blood Transfnsion V
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INDUCTION VCR + PRED + ASNASE (wk 3
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SCHED.INT 1 MTX • ! Adria MTX •
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~ looh---------ooooc>----o---c>----
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Consoll- Irra .tlon t) .tlon Indu
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Highrisk Standard risk Table 1. Cli
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Cumulo/ive comp/el9 remission 1.0 .
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10° 8 = 6 ö 4 Non T Cell .~ :ö
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% SURVIVAL 100 ~ ~II 0 80 60 40 - -
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a) Percentage of donor cell mitoses
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Table 5. Results of bone marrow tra
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...... w N Table 7. Clinical result
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agent had to be added and that in t
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C. Chronic Myelogenous Leukemia The
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Patients with a suitable donor rece
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No. Recurrent Leukaemia Other death
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followed by dialysis against isoton
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HS, HL- Heme >_ 40 0 HS I ;:. =====
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knowing at present. These genes may
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esistance to antifolates. In Vitro
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a DNA probe specific for the gene t
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translocation between chromosomes 9
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Table 1. Subdivision of 1827 Myelo-
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NORMAL CELL ®
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some change of the primary type, in
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F. Transformation of Mouse Bone Mar
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were carried out with 3H-MTX in the
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the lysozyme cDNA prepared from ovi
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et al. 1976). The BJAB cellline in
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dalton bands corresponding to light
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1979). The EBV-carrying cell lines
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producer lines (DAUDI and P3HR-1),
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G, Giovanella B, Westman A, Stehlin
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Dc;bt CT + i J.I9 Raji; 1. i .. 100
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c. Discussion During infectious mon
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C. Nonepisomal Viral DNA We have us
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A 260 3.0 A B 1670 70 N2 2.0 c: E .
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vivo. Nature 260:302-306 - Kirk JTO
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Fig. 1. a Polyacrylamide gelelectro
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1979). The lymphocyte subpopulation
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lysin 0 antigens are found, and mix
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Pope JH (1978) Long-term T cell-med
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Haematology and Blood Transfnsion V
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Charaeteristie Morphologie maturati
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after TPA-induction (Table 3). The
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PA (1978) Reactivity of a rabbit an
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Blood Monocyte. B lood Monocytes 1-
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and nonhistone proteins can serve a
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The findings of the evaluation of s
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Fig. 3. Tumor grawth of L 428 cells
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Cell biological and Immunological A
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consideration. Sanel (1973) obtaine
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endotoxin serum, were used. A parti
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monocytic leukemia cell line in cul
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B. Isolation, Characterization and
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don al hemopathies generally displa
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nitors. Blood Cells 6:595-607 - Min
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\I) ....I ....I IU Jl 200 r 100 90
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their haemopoietic cells' ability t
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normal normal ALL ALL ALL persons p
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64.5 { V)
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References Biermann E, Neth R, Gros
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ehambers, the growth pattern observ
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References Anderssen LC, 10kinen M,
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REH CELL UNE TO CALLb~Ö ~q~ V.M. c
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the macrophage series in which the
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Table 1. Production of factor depen
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Table 1. Characteristics of the adh
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Fig. 3. A human marrow culture at 6
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300 250 • HYPERPROLIFERATIVE PATT
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Fig. 9. Nonadherent population from
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The cobblestone areas were often no
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L (1976) Induction of colony format
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B. Materials and Methods J. Tissue
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Fig. 2. Ultrastructural appearance
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Table 1. Monoclonal antibody reacti
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al. 1979; Janossy et al. 1979) is e
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to which this is an exact replica o
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inger JL (1976) Distribution of la-
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I region antigens were found to be
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have been reported to be present on
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V. FunctionalAssays Assays for PHA
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Functional studies of UCHT1 separat
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40 ,...... (5 L.. C o u 30 .9 ~ .~
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with immunohistochemieal methods (L
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can be dissected by cloning. Utiliz
Page 335 and 336: Table 1. Origin and marker profile
Page 337 and 338: Haematology and Blood Transfusion V
Page 339 and 340: complete identity of gp 100 from no
Page 341 and 342: Table 1. Reaction of single anti se
Page 345 and 346: media. Following 24-h incubation, c
Page 347 and 348: nonleukemic eells (Greaves 1979). L
Page 351 and 352: Fig. 2. Cytocentrifuged smears of b
Page 353 and 354: Modification of amino-groups of hum
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Page 359 and 360: of the EBV infected B cells. Howeve
Page 361 and 362: and immunoglobulins. J Immunol 120:
Page 363 and 364: " K 10 • j ~ ALL RNlL AL wtfh les
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Page 367 and 368: D. Results and Discussion J. Acute
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Page 375 and 376: Table 2. Growth inhibition of S49 e
Page 377 and 378: Reverse Infectious ASC/2X1Q6 transc
Page 381 and 382: munized animals to 1316 tumor cells
Page 383 and 384: Haematology and Blood Transfnsion V
Page 385: Fig. 3. Expression of retroviral gp
Page 389 and 390: Table 1. Expression of tumor antige
Page 391 and 392: Virological and Molecularbiological
Page 393 and 394: Table 1. Oncogenic properties of re
Page 395 and 396: also Fig. 1). It followed that the
Page 397 and 398: whether this sequence is related to
Page 399 and 400: zed in infected cells argue that th
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Page 403 and 404: detect viral RNA as the only charac
Page 405 and 406: Eisen H (1980) Myeloproliferate vir
Page 407 and 408: p,60- -34K - 1 2 3 4 Fig. 1. In vit
Page 409 and 410: .. p - • a'T ... I .t'l Fig. 4. D
Page 413 and 414: Fig. 2. Photomicrographs of NY68 in
Page 415 and 416: DEAE (o(lJmn 'liI GI -2 2 o e s 1
Page 417 and 418: vity was deterrnined. For endogenou
Page 419 and 420: pr 180 - - - P 12/15 - A B c D E F
Page 421 and 422: 85,- 66- -27 - -66 40- 27- -1'9 19-
Page 425 and 426: = 0.5 o E Q. o ILI 0.4 (J) « ILI .
Page 427 and 428: Table 1. Oncogenic potential of avi
Page 429 and 430: 100 III GI c: o "8 80 > w
Page 431 and 432: Expt. No. Infecting virus Proportio
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Page 435 and 436: sequences, provided its gag portion
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77:3009-3013 - Hu SSF, Moscoviei C,
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RI 2.2 md and Hind III 2.6 md leuke
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RELATIONSHIP OF ENDOGENOUS AND EXOG
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E ........ E Cl. U E :::l .... Q) (
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References Astrin S (1978) Endogeno
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the same animal were examined (e.g.
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I) 'IQ a \0 - CL -- Fig. 2. Restrie
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~ ..................... ~ Cell 3' 5
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a :Sa,C! + . ~ 111 i' ( " '~ .J. b
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Table 1 Sampie Tissue TS fragment"
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a b Sac I / rep ._-_.-_ K J nl rep
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Haematology and Blood 'fiansfusion
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Osteopetrosis and osteosarcomas occ
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Lymphoma cellline Table 1. T and B
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Table 2. In vivo growth and oneogen
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Table 1. Transforming aetivity of c
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Table 3. Transformation aetivity of
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- Shoemaker C, Goff S, Gilboa E, Pa
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indieate a shifting of target eell
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Table 2. Expression of Jl and Sourc
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~ i ,..1---------,,':::::::::::::::
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fragment of pBR322 DNA, a 3.0-kbp S
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Mak TW (1979) Proc Natl Acad Sci US
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Table 1. Transformation of 3T3 cell
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inserts in the genome of rapidly tr
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pulations, it seemed likely that th
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contains antigens which react with
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le of reacting in sensitive radioim
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gic approach. In: Hiatt HH, Watson
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12 Eco R [ Fig. 1. Hybridization pa
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10 - '1~ )( -~ S:! E A U I o 1 2
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Haematology and Blood 'fransfusion
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cultures. These cells did not conta
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indication of malignant T-cells in
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Fig. 3. Thin-section electron micro
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Table 3. Lack of detectable related
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J. HTLV Was Present in the Primary
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specific signals into nonspecific s
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Table 2. Distribution of HTLV-relat
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u 10 ~ 20 ~ :c 30 a 40 o Fig. 1. Ki
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SSV TrS-gp labeled effectively with
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60 HFF/SSV cDNA CELL RNAs: 0 HF/SSV
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Antisera a Table 1. Immunofluoresce
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Haematology and Blood 'ftansfusion
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y competition RIA yielded virtually
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SiS'V' gp70: ANTIGEN, ANTI BODY, IM
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type-C virus p30 antigen in cells f
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c. Results The fractionated whole-b
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induced antibodies as well as exper
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- Fig. la-f. Retravirus particles p
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eplication of infecting murine leuk
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immunodeficiency, multic10nal lymph
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Bovine leukemia --, proteins of 499
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Human T- cell - -, characterization
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RNA -, of tumor virus 439 Rous sarc
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Haematology andBlood Transfusion Su
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