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1400 1200 1000 800 600 Unlnhlblted 0--0 Ami Sera -- CII Sera 0--0 Remission Sera __ Non- Leukemlc Sera 400 1 2 3 4 5 Patient' s Sera (Log 2 Titre) Fig. 1. Inhibition of coprecipitation by patient's sera. Sera from AML patients with high blast counts inhibit the precipitation of leukemic antigen by monkey antimyeloblast sera. Significant inhibition is obtained at the first dilution of patient's sera (P50,OOOlmm 3 ), five patients with chronic lymphocytic leukemia (lymphocyte count >50,OOOlmm 3 ), five patients with AML in remission, and five patients with nonleukemic disease. Significant inhibition was seen with low dilutions of sera from patients with high myeloblast counts (P
nonleukemic eells (Greaves 1979). Leukemic blast eells earry oneofetal antigens (Granatek et al. 1976) or antigens eharaeteristic of specific phases of the cell cyde (Pasternak et al. 1974), and these may be recognized by the antiserum. Selective reactivity against myeloblasts may be explained by cell surface glycoprotein changes characteristic of leukemic cells (Andersson et al. 1979; Khilanani et al. 1977; van Beek et al. 1978). Van Beek et al. (1978) have doeumented struetural differences in fucose-containing glycopeptides in leukemic myeloblasts compared to nonleukemic leukocytes, and Andersson et al. (1979) have demonstrated surface glycoprotein patterns diagnostic of acute myeloblastic leukemia. Studies of serum and urine of patients with AML have yielded characteristic compounds resulting from alteration of normal glycoproteins (Rudman et al. 1976). Since the compounds obtained in the present study were not prepared by adding proteolytic or dissociating agents but were rather shed into the supernatant during short-term incubation, we have characterized material that is associated with the cell surface but is not likely to be an integral membrane glycoprotein; furthermore, it may represent intact native compounds rather than fragments. We have previously described the detection of leukemic antigen in the bone marrow of patients with AML in remission (Baker et al. 1979). The increase in reactivity which occurs in marrow before relapse may allow the early use of reinduction chemotherapy. The technical difficulties inherent in studying fresh bone marrow specimens have led us to study antigen levels in serum. Further refinement of immunologie assays for detection of antigen in serum may allow trials of therapeutic intervention upon early deteetion of inerease in tumor burden. References Abraham CV, Bakerman S (1977) Isolation and purification of Rh receptor component from human erythrocyte membrane by isoelectric focusing. Sci Tools 24:22-24 - Andersson LC, Gahmberg CG, Siimes MA, Teerenhoui L, Vuopio P (1979) Cell surface glycoprotein analysis: a diagnostic tool in human leukemias. Int J Cancer 23: 306-311-Baker MA, Ramachandar K, Taub RN (1974) Specificity of heteroantisera to human acute leukemia-associated antigens J Clin Invest 54: 1273-1278 - Baker MA, Falk RE, Falk J, Greaves MF (1976) Detection of monocyte specific antigen on human acute leukemia cells. Br J Haematol 32: 13-19 - Baker MA, Falk JA, Taub RN (1978) Immunotherapy of human acute leukemia: Antibody response to leukemia-associated antigens. Blood 52: 469-480 - Baker MA, Falk JA, Carter WH, Taub RN, and the Toronto Leukemia Study Group: Early diagnosis of relapse in acute myeloblastic leukemia. N Engl J Med 301: 1353-1357 - Billing R, Terasaki TI (1974) Human leukernic antigen. H. Purification. J Natl Cancer Inst 53: 1639-1643 - Cone RE, Marchalonis 11, Rolley RT (1971) Lymphocyte membrane dynamies. Metabolic release of cell surface proteins. J Exp Med 134:1373-1384 - Delepelaire P, Chua N-H (1979) Lithium dodecyl sulfate/polyacrylamide gel electrophoresis of thylakoid membranes at 4°C: Characterization of two additional chlorophyll a-protein complexes. Proc Natl Acad Sei USA 76: 111-115 - Granatek CH, Hanna MG Jr, Hersh EM, Gutterman JU, Mavligit GM, Candler EL (1976) Fetal antigens in human leukemia. Cancer Res 36:3464-3470 - Greaves MF (1979) Cell surface characteristics of human leukemic cells. In: Langsben PN, Marshall RD (eds) Essays in biochemistry, vol 15. Acadernic Press, New York, p 78 - Gutterman JU, Mavligit G, McCredie KB, Bodey GP Sr, Freireich EJ, Hersh EM (1972) Human leukemia antigens: Partial isolation and characterization. Seience 177:1114-1115 - Hubbard A, Cohen Z (1972) The Enzymatic iodination of the red cell membrane. J Cell Biol 55: 390-405 - Humphreys RE, McCune JM, Chess L, Herrman HC, Malenka DJ, Mann DL, Parharn P, Schlossman SF, Strominger JL (1976) Isolation and immunologic characterization of a human, B-Iymphocyte-specific, cell surface antigen. J Exp Med 144: 98-112 - Khilanani P, Chou T-H, Lomen PL, Kessel D (1977) Variations of levels of plasma guanosine diphosphate L-Fucose: ß-D galactosyl a-2-L-Fucosyl-transferase in acute adult leukemia. Cancer Res 37:2557-2559 - Laemmli U (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685 - Mavligit DM, Ambus U, Gutterman JU, Hersh EM, McBride CM (1973) Antigens solubilized from human solid tumors: Lymphocyte stimulation and cutaneous delayed hypersensitivity. Nature [New Biol] 243 : 183-186 - Metzgar RS, Mohanakumar T, Green RW, Miller DS, Bolgonesi DP (1974) Human leukemia antigens: Partial isolation and characterization. J Natl Cancer Inst 52: 1445-1453 - Mittal KK, Mickey MR, Singal DP, Terasaki PI (1968) Serotyping for homotransplantation. XVIII. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation 6:913-927 - Mohanakumar T, Metzgar RS, Miller DS (1974) Human leukemia cell antigens: Serological characterization with xenoantisera. J Natl Cancer Inst 52: 1435-1444 - Mohanakumar T, Giedlin M, Du Vall C, Rhodes C, Phibbs M, Mendez G, Kaplan AM, Lee HM (1979) B-lympho- 336
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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
Page 295 and 296: Fig. 9. Nonadherent population from
Page 297 and 298: The cobblestone areas were often no
Page 299 and 300: L (1976) Induction of colony format
Page 301 and 302: B. Materials and Methods J. Tissue
Page 303 and 304: Fig. 2. Ultrastructural appearance
Page 305 and 306: Haematology and Blood Transfusion V
Page 309 and 310: Table 1. Monoclonal antibody reacti
Page 311 and 312: al. 1979; Janossy et al. 1979) is e
Page 313 and 314: to which this is an exact replica o
Page 315 and 316: inger JL (1976) Distribution of la-
Page 317 and 318: I region antigens were found to be
Page 319 and 320: have been reported to be present on
Page 321 and 322: V. FunctionalAssays Assays for PHA
Page 323 and 324: Functional studies of UCHT1 separat
Page 327 and 328: 40 ,...... (5 L.. C o u 30 .9 ~ .~
Page 329 and 330: with immunohistochemieal methods (L
Page 333 and 334: can be dissected by cloning. Utiliz
Page 335 and 336: Table 1. Origin and marker profile
Page 339 and 340: complete identity of gp 100 from no
Page 341 and 342: Table 1. Reaction of single anti se
Page 345: media. Following 24-h incubation, c
Page 351 and 352: Fig. 2. Cytocentrifuged smears of b
Page 353 and 354: Modification of amino-groups of hum
Page 355 and 356: disturb this balance in the directi
Page 357 and 358: The majority of human blood lymphoc
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
Page 365 and 366: tion akuter Leukämiezellen in "spo
Page 367 and 368: D. Results and Discussion J. Acute
Page 369 and 370: selectively responsive to different
Page 373 and 374: l1J ~ 100 ~ Q. ::) l1J Z 0 ~ z >- .
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 and 386: Fig. 3. Expression of retroviral gp
Page 387 and 388: pg70. J Exp Med 143: 151-166 - McGr
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
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whether this sequence is related to
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zed in infected cells argue that th
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a specific viral transforming prote
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detect viral RNA as the only charac
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Eisen H (1980) Myeloproliferate vir
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p,60- -34K - 1 2 3 4 Fig. 1. In vit
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.. p - • a'T ... I .t'l Fig. 4. D
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Fig. 2. Photomicrographs of NY68 in
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DEAE (o(lJmn 'liI GI -2 2 o e s 1
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vity was deterrnined. For endogenou
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pr 180 - - - P 12/15 - A B c D E F
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85,- 66- -27 - -66 40- 27- -1'9 19-
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= 0.5 o E Q. o ILI 0.4 (J) « ILI .
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Table 1. Oncogenic potential of avi
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100 III GI c: o "8 80 > w
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Expt. No. Infecting virus Proportio
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Haematology and Blood 'fransfusion
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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) (
Page 447 and 448:
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
Page 537 and 538:
Antisera a Table 1. Immunofluoresce
Page 539 and 540:
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
Page 563 and 564:
RNA -, of tumor virus 439 Rous sarc
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Haematology andBlood Transfusion Su
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