Summary
Leukocyte-derived inhibitory activity inhibiting the entry of normal progenitor cells of granulocytes and macrophages (CFU-GM) into the S-phase of a cell cycle was investigated in 16 patients with different forms of myelodysplastic syndrome (MDS). The presence of this inhibitory activity was analysed in medium conditioned with low-density cells obtained from peripheral blood of MDS patients. The inhibition rate was measured by 3H-thymidine suicide technique with subsequent cultivation of pretreated cells in semisolid agar medium. Low-density cells from MDS patients of various types were studied: from the twelve patients with refractory anaemia (RA or RAS) only three were positive, one patient with chronic myelomonocytic leukaemia (CMML) was negative while one patient with refractory anaemia with excess of blasts (RAEB) and two patients with RAEB in transformation (RAEB-T) were positive with respect of the described test. In two patients with RA, who underwent a long-term investigation, the production of leukocyte-derived inhibitory activity preceded the development of disease into RAEB or RAEB-T. In five positive cases, supernatants were incubated with antiserum against human placental ferritin; with one exception, the inhibitory activity was neutralized.
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Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HP, Sultan C (FAB Cooperative Group) (1982) Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51: 189–199
Broxmeyer HE, Jacobsen N, Kurland J, Mendelsohn N, Moore MAS (1978) In vitro suppression of normal granulocytic stem cells by inhibitory activity derived from human leukemia cells. J Nat Cancer Inst 60: 497–511
Broxmeyer HE, Bognacki J, Dorner MH, De Sousa M (1981) Identification of leukemia-associated inhibitory activity as acidic isoferritins. J Exp Med 153: 1426–1444
Chui DHK, Clarke BJ (1982) Abnormal erythroid progenitor cells in human preleukemia. Blood 60: 362–367
Cukrová V, Hrkal Z, Kopřivová H, Neuwirt J (1986) Identification of Leukemia Cell-Derived Inhibitory Activity (LIA) in Conditioned Media from Human Myeloid Leukemic Cell Line ML-2. Blut 52: 51–58
Galton DAG (1984) The myelodysplastic syndromes. Clin Lab Haematol 6: 99–112
Greenberg P, Mara B, Bax I, Brossel R, Schrier S (1976) The myeloproliferative disorders: Correlation between clinical evolution and alterations of granulopoiesis. Am J Med 61: 878–891
Greenberg PL (1983) The Smoldering Myeloid Leukemic States: Clinical and Biological Features. Blood 61: 1035–1044
Guilbert LJ, Iscove NN (1976) Partial replacement of serum by selenite, transferrin, albumin and lecithin in haematopoietic cell cultures. Nature 263: 594–595
Faille A, Dresch C, Poirier O, Balitrand N, Najean Y (1978) Prognostic value of in vitro bone marrow culture in refractory anaemia with excess of myeloblasts. Scand J Haematol 20: 280–286
Francis GE, Wing MA, Miller EJ, Berney JJ, Wonke B, Hoffbrand AV (1983) Use of bone-marrow culture in prediction of acute leukaemic transformation in preleukemia. Lancet 1: 1409–1412
Jacobs A (1983) Do Acidic Isoferritins Regulate Haemopoiesis. Br J Haematol 55: 199–202
Jelínek J, Neuwirt J, Neuwirtová R (1986) Clonal Cultivation of Haemopoietic Cells in Patients with Myelodysplastic Syndrome (Vnitřní lékařství) Int Med 32: 222–227 (English summary)
Koeffler HP, Cline MJ, Golde DW (1978) Erythropoiesis in preleukemia. Blood 51: 1013–1019
Miller EJ, Francis GE, Wing MA, Berney JJ, Wonke B, Hoffbrand AV (1983) Bone marrow culture in prediction of acute leukemic transformation of “pre-leukaemia”. Br J Haematol 55: 175
Olofsson T, Olsson I (1980) Suppression of normal granulopoiesis in vitro by a leukemia associated inhibitor (LAI) derived from human promyelotic cell line (HL-60). Leuk Res 4: 437–447
Pierre R, Sultan C, Vardiman J (1982) The myelodysplastic syndromes. Hematology — educational program. Washington 1–5
Ruutu T, Partanen S, Lintula R, Teerenhovi L, Knuutila S (1984) Erythroid and granulocyte-macrophage colony formation in myelodysplastic syndromes. Scand J Haematol 32: 395–402
Sala G, Worwood M, Jacobs A (1986) The Effect of Isoferritins on Granulopoiesis. Blood 67: 436–443
Scoazec J, Imbert M, Crofts M, Jouault H, Juneja SK, Vernant J, Sultan C (1985) Myelodysplastic Syndrome or Acute Myeloid Leukemia? Cancer 55: 2390–2394
Senn JS, Pinkerton PH (1972) Defective in vitro colony formation by human bone marrow preceding overt leukemia. Br J Haematol 23: 277–282
Senn JS, Messner HA, Pinkerton PH, Chang L, Nitsch B, McCulloch EA and the Toronto Area Preleukemia Study Group (1982) Peripheral blood blast cell progenitors in human preleukemia. Blood 59: 106–109
Verma DS, Spitzer G, Dicke KA, McCredie KB (1979) In vitro agar culture patterns in preleukemia and their clinical significance. Leuk Res 3: 41–49
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Cukrová, V., Neuwirtová, R., Čermák, J. et al. Leukocyte-derived inhibitory activity in patients with myelodysplastic syndrome. Blut 55, 165–171 (1987). https://doi.org/10.1007/BF00320571
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DOI: https://doi.org/10.1007/BF00320571