Summary
We used the human placental conditioned medium stimulated single layer agar culture technique to study the in vitro growth of marrow cells from 62 adult patients with acute myeloid leukemia (AML). Bone marrow cells were cultured from 50 patients at the time of initial diagnosis, 19 patients in early remission and 20 patients during their full complete remission. Marrow cultures from untreated patients exhibited heterogeneous growth patterns ranging from complete growth failure to excessive microcluster formation. We classified the growth patterns into 4 groups: (1) Gr I: normal growth, (2) Gr II: no growth, (3) Gr III: decreased growth, (4) Gr IV: excessive growth of microclusters. At presentation, none had Gr I growth; Gr II growth was observed in 23; Gr III in 14 and Gr IV in 13. A predominance of no growth were seen in M1 and M3 subtypes, while Gr IV growth was more commonly observed in M2 or M4 subtype. We were unable to correlate the culture findings with age or white cell count. The present results not only indicated that AML at diagnosis was characterized by abnormal granulopoiesis but also demonstrated that leukemic progenitor cells were heterogeneous with different capacities to express their proliferating potential in vitro. Except few with decreased growth, the growth characteristics generally returned to normal with successful remission induction. Both Gr II and Gr IV growth patterns were not observed either in early remission or during full complete remission.
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References
Barak Y, Ma A, Shore NA (1979) Acute myelomonocytic leukemia in children. Acta Haematol 62: 137–142
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of the acute leukemias. Br J Haematol 33: 451–458
Beran M, Reizenstein P, Uden AM (1980) Response to treatment in acute non-lymphatic leukaemia: prognostic value of colony forming and colony stimulating capacities of bone marrow and blood cells compared to other parameters. Br J Haematol 44: 39–50
Brown CH, Carbone PP (1971) In vitro growth of normal and leukemic human bone marrow. J Nat Cancer Inst 46: 989–1000
Bull JM, Duttera MJ, Stashick ED, Northup J, Henderson E, Carbone PP (1973) Serial in vitro marrow culture in acute myelocytic leukemia. Blood 42: 679–686
Burgess AW, Wilson EMA, Metcalf D (1977) Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells. Blood 49: 573–583
Curtis JE, Cowan DH, Bergsagel DE, Hasselback R, McCulloch EA (1975) Acute leukemia in adults: assessment of remission induction with combination chemotherapy by clinical and cell-culture criteria. CMA J 113: 289–294
Duttera MJ, Bull JM, Northup JD, Henderson ES, Stashick ED, Carbone PP (1973) Serial in vitro bone marrow culture in acute lymphocytic leukemia. Blood 42: 687–699
Eridani S, Sawyer B, Batten E (1983) Haemopoietic patterns of leukaemia in remission: CFU-E and CFU-GM colony formation. Acta Haematol 70: 11–18
Goldberg J, Tice D, Nelson DA, Gottlieb AJ (1979) Predictive value of in vitro colony and cluster formation in acute nonlymphocytic leukemia. Am J Med Sci 277: 81–84
Greenberg PL (1980) Clinical relevance of in vitro study of granulopoiesis. Scand J Haematol 25: 369–381
Greenberg PL, Nichols WC, Schrier SL (1971) Granulopoiesis in acute myeloid leukemia and preleukemia. N Engl J Med 284: 1225–1232
Gustavsson A, Mitelman F, Olofsson T, Olsson I (1984) The relationship between growth in agar, karyotype and prognosis in acute leukaemia. Scand J Haematol 32: 351–363
Hörnsten P, Gahrton G, Sundman S, Wahren B (1982) In vitro colony studies in 87 patients with acute nonlymphoblastic leukemia. Acta Med Scand 211: 195–201
Hörnsten P, Lindquist R, Gahrton G (1984) Prognostic implications of in vitro colony studies and clonal chromsomal aberrations in adults with acute leukaemia. Scand J Haematol 32: 297–305
Iscove NN, Senn JS, Till JE, McCulloch EA (1971) Colony formation by normal and leukemia human marrow cells in culture: effect of conditioned medium from human leukocytes. Blood 37: 1–5
Knudtzon S (1977) In vitro culture to leukaemic cells from 81 patients with acute leukaemia. Scand J Haematol 18: 377–394
Mertelsmann R, Moore MAS, Broxmeyer HE, Cirrincione C, Clarkson B (1981) Diagnostic and prognostic significance of the CFU-C assay in acute nonlymphoblastic leukemia. Cancer Res 41: 4844–4848
Metcalf D, Moore MAS, Sheridan JW, Spitzer G (1974) Responsiveness of human granulocytic leukemic cells to colony-stimulating factor. Blood 43: 847–859
Moore MAS (1975) Marrow culture: a new approach to classification of leukemias. Blood Cells 1: 149–158
Moore MAS, Spitzer G, Williams N, Metcalf D, Buckley J (1974) Agar culture studies in 127 cases of untreated acute leukemia: the prognostic value of reclassification of leukemia according to in vitro growth characteristics. Blood 44: 1–18
Moore MAS, Williams N, Metcalf D (1973) In vitro colony formation by normal and leukemic human hematopoietic cells: characterization of the colony-forming cells. Cancer Res 50: 603–623
Richman CM, Rowley JD (1983) Correlation of in vitro culture pattern and Q-banded karyotype in acute nonlymphocytic leukemia. Am J Hematol 14: 37–47
Richman CM, Weiner RS, Yankee RA (1976) Increase in circulating stem cells following chemotherapy in man. Blood 47: 1031–1039
Robinson WA, Kurnick JE, Pike BL (1971) Colony growth of human leukemic peripheral blood cells in vitro. Blood 38: 500–508
Senn JS, Curtis JE, Pinkerton PH, Till JE, McCulloch EA, the Toronto area preleukemia group (1980) The distribution of marrow granulopoietic progenitors among patients with preleukemia. Leuk Res 4: 409–413
Senn JS, McCulloch EA (1970) Kinetics of regeneration after cyclophosphamide in human marrow assessed by a cell culture method. Exp Hematol 20: 8–9
Senn JS, McCulloch EA, Till JE (1967) Comparison of colony-forming ability of normal and leukaemic human marrow in cell culture. Lancet 2: 597–598
Shih LY, Chang CY (1984) Stimulation of colony formation of human hemopoietic cells with human placental conditioned medium. J Formosan Med Assoc 83: 934–941
Spitzer G, Dicke KA, Gehan EA, Smith T, McCredie KB (1976) The use of the Robinson in vitro agar culture assay in adult acute leukemia. Blood Cells 2: 139–148
Spitzer G, Dicke KA, Gehan EA, Smith T, McCredie KB, Barlogie B, Freireich EJ (1976) A simplified in vitro classification for prognosis in adult acute leukemia: the application of in vitro results in remission-predictive models. Blood 48: 795–807
Spitzer G, Verma DS, Dicke KA, McCredie KB (1978) Culture studies in vitro in human leukemia. Semin Hematol 15: 352–378
Vincent PC, Sutherland R, Bradley M, Lind D, Gunz FW (1977) Marrow culture studies in adult acute leukemia at presentation and during remission. Blood 49: 903–912
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Shih, LY., Chang, CY. Marrow culture studies in adult acute myeloid leukemia at diagnosis and during complete remission. Blut 50, 225–232 (1985). https://doi.org/10.1007/BF00320299
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DOI: https://doi.org/10.1007/BF00320299