Table Of ContentModern Trends in Human Leukemia II
Biological, Immunological, Therapeutical and Virological Aspects
Hamatologie und Bluttransfusion
Herausgegeben von W. Stich, G. Ruhenstroth-Bauer und H. Heimpel
Sonderbande zu Blut . Zeitschrift fur die gesamte Blutforschung
Organ der Deutschen Gesellschaft fur Hamatologie
Organ der Deutschen Gesellschaft fur Bluttransfusion
Band 19
J. F. Lehmanns Verlag MOnchen
Modern Trends
in Human Leukemia II
Biological, Immunological, Therapeutical and Virological Aspects
Edited by
Rolf Neth
Molekularbiologisch-hama tologische Arbei tsgru ppe
U niversi tats-Kinderklinik
Hamburg-Eppendorf, W. Germany
Robert C. Gallo
Laboratory of Tumor Cell Biology
Division of Cancer Treatment
National Cancer Institute
National Institutes of Health
Bethesda, Maryland, USA
Klaus Mannweiler
Heinrich-Pette-Institut fur experimentelle Virologie
und Immunologie an der Universitat Hamburg
Hamburg-Eppendorf, W. Germany
William C. Moloney
Harvard Medical School
Department of Medicine
Hematology Division
Boston, Massachusetts, USA
J. F. Lehmanns Verlag Munchen
We should like to thank alI those in Germany and the USA who made this work
shop possible:
Stiftung Volkswagenwerk, Hannover
National Cancer Institute, National Institutes of Health, Bethesda,Maryland, USA
Deutsche Gesellschaft fiir Hămatologie
Hamburgische Wissenschaftliche Stiftung, Hamburg
Hertha-Grober-Stiftung, Hamburg
Paul-Martini-Stiftung, Frankfurt
Universităts-GeselIschaft Hamburg
We thank the Behorde fiir Wissenschaft und Kunst der Freien und Hansestadt Ham
burg, the lord mayor of Liineburg, the 5tiftung F. V. S. zu Hamburg and the
Amerikahaus in Hamburg for their generous hospitality.
We thank Miss D. Dirks for proof-reading of the manuscripts and translational
help.
We thank the publisher J. F. Lehmanns Verlag and the Druckerei Poeschel & Schulz
Schomburgk for prompt and conscious collaboration.
© J. F. Lehmanns Verlag Miinchen 1976
Alle Rechte vorbehalten
Gesamtherstellung: Druckerei Poeschel & Schulz-Schomburgk, 344 Eschwege/Werra
ISBN 978-3-540-79785-2 ISBN 978-3-642-87524-3 (eBook)
DOI 10.1007/978-3-642-87524-3
Frederick Stohlmann Workshop: Modern Trends in Human Leukemia II
"De Emhoff" in Wilsede, Naturschutzpark LUneburger Heide
June 23rd to 27th, 1975
On behalf of the Deutsche Gesellschaft fUr Hamatologie
and the National Cancer Institute
the workshop was organized by
Rolf Neth
Molekularbiologisch-hamatologische Arbeitsgruppe
Universitats-Kinderklinik
Hamburg-Eppendorf, W. Germany
Robert C. Gallo
Laboratory of Tumor Cell Biology
Division of Cancer Treatment
National Cancer Institute
National Institutes of Health
Bethesda, Maryland, USA
Klaus Mannweiler
Heinrich-Pette-Institut fUr experimentelle Virologie und Immunologie an der
Universitat Hamburg
Hamburg-Eppendorf, W. Germany
Frederick Stohlmann, Jr. t
St. Elizabeth's Hospital of Boston
Tufts University Medical School
Boston, Massachusetts, USA
v
Contents
Cell Biology of Leukemia
Cronkite, E. P.: Notions about the hemopoietic stem cell . . . . . . . .
Fliedner, T. M., Hoelzer, D., Steinbach, K. H.: Productivity in normal and
leukemic granulopoiesis .................... 9
Beckmann, H., Neth, R., Soltau, H., Mertelsmann, R., Winkler, K., Haus
mann, K., Hellwege, H., Skrandies, G.: Cytology and cytochemistry
of colony cells in soft agar gel culture from normal and leukemic bone
marrow . . . . . . . . . . . . . . . . . . . . . . . . . .. 21
Till, j. E., Mak, T. W., Price, G. B., Senn, j. S., McCulloch, E. A.: Cellular
subclasses in human leukemic hemopoiesis . . . . . . . . . . . .. 33
Walther, F., Schubert, j. C. F., Schopow, K.: Characterisation and patholog-
ical growth of human bone marrow cells by means of a new stem cell assay 47
Wu, A. M., Gallo, R. C.: The phenotypic abnormality in leukemia: a de-
fective cell-factor interaction? . . . . . . . . . . . . . . . . .. 51
Dicke, K. A., Spitzer, G., Scheffers, H. M., Cork, A., Ahearn, M. j., Lowen-
berg, B., McCredie, K. B.: In vitro colony growth of acute myelogenous
leukemia . . . . . . . . . . . . . . . . . . . . . . . . . .. 63
¥oore, M. A. S.: Clinical utility of bone marrow culture . . . . . . .. 79
Dormer, P.: Proliferative behavior of hemopoietic cells in preleukemia and
overt leukemia observed in one patient . . . . . . . . . . . . .. 91
Parwaresch, M. R., Muller-Hermelink, H. K., Lennert, K.: Leukemic an-
aplasias reflecting physiologic cytogenesis of myeloid system . . . .. 95
Shohet, S. B.: Membrane remodeling during phagocytosis in chronic myel-
ogenous leukemia cells . . . . . . . . . . . . . . . . . . 101
Forget, B. G., Glass, j., Housman, D.: Erythroid cell differentiation 108
Paul, j.: Molecular mechanisms in erythroid differentiation . . . . 125
Arndt-jovin, D. j., Ostertag, W., Eisen, H., jovin, T. M.: Analysis by com-
puter controlled cell sorter of Friend virus-transformed cells in different
stages of differentiation ..... . . . . . . . . . . . . . .. 137
Nooter, K., Ghio, R., v. d. Berg, K. j., Bentvelzen, P. A. j.: Hormone inde-
pendent in vitro erythroid colony formation by mouse bone marrow cells 151
Preisler, H. D.: In vitro and preliminary in vivo studies of compounds which
induc:e the differentiation of Friend leukemia cells . . . . . . . . .. 161
VI
Graf, T., Royer-Pokora, B., Beug, H.: Target cells for leukemic transfor-
mation by chicken C-type viruses . . . . . . . . . . 169
Watkins, j. F.: Fusion experiments with human tumour cells . . . . .. 177
Kelly, F.: Effect of cytochalasin B on malignant cells . . . . .. 181
Stiles, C. D., Roberts, P. E., Saier, M. H., Sato, G.: Growth regulation and
suppression of metastasis in the congenitally athymic nude mouse 185
Immunology of Leukemia
Herberman, R. B.: Cell-mediated immunity to leukemia associated antigens
in experimental models and in man . . . . . . . . . . . . . .. 195
Gourdin, M. F., Reyes, F., Lejonc, j. L., Mannoni, P., Dreyfus, B.: Surface
features of cells in human lymphoproliferative disorders. An immuno-
electron microscopy study . . . . . . . . . . . . . . . . . . .. 207
Brouet, j. C., Chevalier, A.: Immunological characterization of blast cells in
patients with acute lymphoblastic leukemias. Evaluation of its clinical
significance . . . . . . . . . . . . . . . . . . . . . . . . .. 221
Kadin, M. A., Gold, S., Garratty, E. M., Stites, D. P.: Immunological mem-
brane markers of Hodgkin's cells . . . . . . . . . . . . . . . .. 229
Billing, R., Rafizadeh, B., Zebrowski, A., Hartman, G., Terasaki, P. I.:
Human leukemia-lymphoma associated antigen detected by heteroantisera 237
Greaves, M., Capellaro, D., Brown, G., Revesz, T., janossy, G.: Analysis of
human leukaemic cells using cell surface binding probes and the fluores-
cence activated cell sorter . . . . . . . . . . . . . . . . . . .. 243
Mitchison, N. A.: Use of immunological reagents prepared in animals to
characterise the surface of leukaemic cells . . . . . . . . . . . .. 261
Therapy of Leukemia
Simone, j. V., Aur, R. J. A., Hustu, H. 0., Verzosa, M.: Trends in the
treatment of childhood leukemia . . . . . . . . . . . . . . . 263
Wiernik, P. H.: The therapy of acute leukemia in the adult. A progress
report . . . . . . . . . . . . . . . . . . . . . . . . . . .. 271
Hocker, P., Pittermann, E., Lutz, D., Stacher, A.: Aids in the management of
leukemia (cell removal by continuos flow leukapheresis and impulse cyto-
photometry) ......................... 285
Powles, R. L., Russell, j. A.: The place of immunological methods of treat-
ment in the management of acute leukaemia . . . . . . . . . . .. 297
Henderson, R. S.: Perspectives and prospectives in the management of acute
leukemia . . . . . . . . . . . . . . . . . . . . . . . . . .. 305
Oncogenic Viruses in Leukemia
Baluda, M. A., Shoyab, M., Ali, M., Markham, P. D., Drohan, W. N.: Re-
VII
stricted addition of proviral DNA in target tissues of chickens infected
with avian myeloblastosis virus . . . . . . . . . . . . . . . .. 311
Duesberg, P. H., Wang, I.-H., Beeman, K., Kawai, S., Hanafusa, H.: Se-
quences and functions of Rous sarcoma virus RNA . . . . . . . .. 327
Jaenisch, R., Dausman, J., Cox, V., Fan, H.: Infection of developing mouse
embryos with murine leukemia virus: tissue specificity and genetic trans-
mission of the virus . . . . . . . . . . . . . . . . . . . . .. 341
Todaro, G. J.: Type C virogenes: modes of transmission and evolutionary
aspects . . . . . . . . . . . . . . . . . . . . . . . . . . .. 357
Kettmann, R., Portetelle, D., Mammerickx, M., Cleuter, Y., Dekegel, D.,
Galoux, M., Ghysdael, /., Burny, A., Chantrenne, H.: Bovine leukemia
virus: an exogenous RNA oncogenic virus? . . . . . . 375
Spiegelman S.: Molecular evidence for the association of RNA tumor
viruses with human mesenchymal malignancies . . . . . . . . . .. 391
Gallo, R. C.: RNA tumor viruses and leukemia: evaluation of present results
supporting their presence in human leukemias . . . . . . . . . .. 431
Tavitian, A., Larsen, C. J., Hamelin, R., Boiron, M.: Murine and simian
C-type viruses: sequences detected in the RNA of human leukemic cells
by the c-DNA probes . . . . . . . . . . . . . . . . . . . .. 451
Laufs, R., Steinke, H.: Prevention of herpes-associated malignancies in pri-
mates: problems and prospects . . . . . . . . . . . . . . . . .. 457
Rapp, F.: New properties of mammalian cells transformed by herpes simplex
and cytomegalo-viruses . . . . . . . . . . . . . . . . . . . .. 461
Diehl, V.: Fallure to immortalize human 'null' cells by Epstein Barr virus
(EBV) 'in vitro' . . . . . . . . . . . . . . . . . . . . . 471
zur Hausen, H.: The role of viruses in human leukemia: a summary 475
RNA Synthesis and Translation in Leukemic Cells
Starlinger, P.: IS-element in bacteria . . . . . . . . . . . . . . .. 481
Mertelsmann, R., Heitbrock, H. W., Garbrecht, M.: Circadian variation of
a-amanitine sensitive RNA-synthesis in normal human lymphocytes .. 485
Sarin, P. S., Gallo, R. c.: Terminal deoxynucleotidyl transferase as a biolog-
ical marker for human leukemia . . . . . . . . . . . . . . . .. 491
McCaffrey, R., Harrison, T. A., Kung, P. c., Parkman, R., Silverstone,
A. E., Baltimore, D.: Terminal deoxynucleotidyl transferase in normal
and neoplastic hematopoietic cells. . . . . . . . . . . . . . . .. 503
Bauer, G., Jilek, G., Hofschneider, P. H.: A new, not virus related reverse
transcriptase in the chi <ken system. . . . . . . . . . . . . . . .. 515
Hardesty, B., Kramer, G., Cimadevilla, M., Pinphanichakarn, P., Konecki,
D.: Translation level control in normal and leukemic cells . . . . .. 531
Koch, G., Oppermann, H., Bilello, P., Koch, F., NU5S, D.: Control of peptide
chain initiation in un infected and virus infected cells by membrane me-
diated events . 541
List of Participants 557
Subject Index 567
VIII
Preface Darin aber zeigt sich der vollkom
mene Stil in jeglicher Kunst, daft er
die spezijischen Schranken derselben
zu entfernen weip, ohne doch ihre
spezijischen Vorzuge mit aufzuhe
ben, und durch eine weise Benut
zung ihrer Eigentumlichkeit ihr
einen mehr allgemeinen Charakter
erteilt.
Friedrich Schiller - Ober die as the
tische Erziehung des Menschen. In
den Horen, 22. Brief (1795)
We are glad that you have all come to this small village and I hope that you will
feel at home here for the next few days. The special atmosphere of the surround
ings will probably have a good influence on our discussions, and you will perhaps
remember this when you are back home again. It takes hard work to save this little
piece of nature for man in our highly industrialized world, and we should all be
grateful to the Verein Naturschutzpark e. V. (founded in 1909), Alfred Toepfer and
his associates for their efforts.
We intend to discuss modern trends in human leukemia in this workshop, but we
should also take the opportunity to reflect on the trends of the past, which might
still be modern.
Rudolf VIRCHOW was the first using the name "leukemia" to express that this
was a disease sui generis. About 125 years ago VIR CHOW wrote the following
words:
"This is what we know about leukemia: During normal blood cell production the
cells differentiate into specific types. In a pathologic situation the differentiation
into specific cells is blocked. This disturbance of normal differentiation - so called
leukemia - is a disease sui generis. We know the sequels of this disease, but we don't
know its origin. As yet there has been no successful case of complete cure."
It is perhaps depressing and certainly a challenge that these words are today as
true as they were in 1849, when they were written. In fact, the origins of human
organic sickness are now as unknown as before. We can, however, help the patient
better than we could a few years ago. Besides cytostatic therapy and supportive
care, the personal efforts of the doctors themselves are the most important factor of
therapy.
As long as there is no leukemia-specific therapy as well as a specific therapy of
other cancers, early diagnosis of the disease appears to be very important. Despite of
the progress in morphologic techniques, the sensitivity of leukemia diagnosis is not
much better than 80 years ago, when Paul EHRLICH developed his staining
technique.
Leukemia is usually diagnosed when it can be recognized in the bone marrow,
i. e. when there are more than 1012 leukemic cells in the patient. But this is already
too late. The reason for this late diagnosis is that leukemic cells cannot be distin
guished morphologically from normal stem cells.
Two years ago, when we had our first workshop on modern trends in human
IX
leukemia, we could give no answer how to find a more sensitive leukemia specific
signal, and we learnt that molecular biologic techniques failed and could not offer
a successful way to help the patient directly.
In the meantime various groups have tried to find leukemic cell membrane
specific antibodies and to use them as a diagnostic signal. The molecular biologists
have critically revised their results. And we hope for a successful virologic research.
Apart from this the clinicians developed during the last years more effective and
promising therapeutic methods - without having a leukemia specific cell marker and
without any knowledge about the origin ofthe disease.
Our workshop's aim is to think about the practical application of our research
and about its use for the patient. It was one of Frederick Stohlman's persuasions
to ask for this practical approach, and he also did when we started together plan
ning this workshop. I think we should all together try to realize this plan, and to
remind us of this aim the second Wilsede meeting will be named "Frederick Stohl
man Workshop". Moreover, all further Wilsede meetings will comprise a "Frederick
Stohlman lecture".
Rolf Neth
Frederick Stohlman, Jr. in the garden of "De Emhoff" during a personal discussion (first ~
workshop, June 1973). Fow: Moldvay (STERN-Magazin)
x
