[en] Human peripheral blood lymphocytes isolated using a Ficoll-Uropolinum gradient were exposed to between 1 and 25 Gy X-rays and were cultured for period of up to 72 hours. Before irradiation and after 2, 24, 48 and 72 hours total numbers of surviving cells per ml of culture were determined as well as the frequencies of cells spontaneously forming rosettes (E) and active rosettes (AE) with sheep red blood cells, cells bearing receptor for activated complement (EAC) and cells spontaneously forming rosettes with mouse red blood cells (ME). Irrespective of the duration of in vitro culture, the radiosensitivity of the subpopulations of human lymphocytes increased in the order E < EAC = ME < AE rosette forming cells. Calculation of the frequencies of surviving cells, null with respect to the surface markers (E and EAC), showed that disappearance of rosette-forming cells under the influence of radiation was largely due to the shedding of their receptors and not exclusively to cell death. It is suggested that the extreme radiosensitivity of the subpopulation of T lymphocytes capable of AE rosette formation, if confirmed by in vivo studies, may possess diagnostic significance in persons accidentally exposed to radiation. (author)

[en] Experience is reported with the treatment of iatrogenic pancytopenia in primary chemotherapy with massive doses of cytostatic drugs, namely alterations of the immune and the blood formation systems. The condition can be considered to be a model of the acute irradiation syndrome, thus allowing to define the principles of diagnosis, prevention and therapy. (L.O.). 10 refs

[en] Marrow cells from ten healthy adult donors were cultured in plasma clot diffusion chambers implanted intraperitoneally into mice. Host animals were conditioned by two injections of phenylhydrazine and 600 cGy of x-rays. Cultures (5 X 10(4) cells/chamber) were continued for between 2 and 40 days and the chambers were retransplanted into new host animals every 5 days. Following termination of cultures, plasma clots were stained with benzidine-hematoxylin and analyzed microscopically. Erythroid, neutrophil, monocyte, eosinophil, megakaryocyte, mixed, undifferentiated, and fibroblastoid colonies were grown with neutrophil, erythroid, monocyte, and eosinophil colonies being the most frequent. A total of between 25 and 60 colonies was observed per chamber at any time point

[en] The hemopoietic regeneration following midlethal irradiation in Wsup(v)/+ mice had similarly biphasic kinetics as in their hematologically normal +/+ littermates. The first abortive phase of regeneration was either severly reduced (formation of transient endogenous spleen colonies, reticulocyte count, granulocyte count) or absent (spleen and femur cellularity, platelet count, PCV) in Wsup(v)/+ mice, when compared to +/+ mice. The second phase leading to permanent recovery of hemopoiesis was in Wsup(v)/+ mice delayed in time. Moreover, although to a lesser extent the values of spleen and femur cellularity, PCV and platelet count were decreased in Wsup(v)/+ mice. Postirradiation bleeding, which stimulated particularly the 1st phase of regeneration both in Wsup(v)/+ and +/+ mice did not lead to the minimization of differences between above two genotypes. It is suggested that the observed differences in the abortive regeneration between Wsup(v)/+ and +/+ mice are primarily dependent on the presence in Wsup(v)/+ mice of selective defect of transient endogeneous colony forming units (TE-CFUs). Moreover, it is possible that the differences in the second phase of regeneration leading to permanent recovery are secondarily dependent on the TE-CFUs defect, as most probably the TE-CFU is the step in stem cell differentiation to mature cells. (orig.)

[en] Normal hematopoietic progenitors and acute myelogenous leukemia cells show a differential requirement for the encoded product of c-myb proto-oncogene for proliferation. To determine whether c-myb is also differentially required for the proliferation of hematopoietic progenitors of chronic myelogenous leukemia (CML), mononuclear cells derived from both chronic phase and blast crisis were exposed to c-myb antisense oligodeoxynucleotides and assayed for colony-forming ability. Exposure of CML-BC cells from 12 patients to c-myb antisense oligodeoxynucleotides resulted in significant inhibition of leukemia colony formation and was accompanied by down-regulation of c-myb expression. Colonies derived from CML chronic phase progenitors were virtually unaffected in 10 cases, but down-regulation of c-myb expression was not detected. However, in studies conducted with CD34+ leukemia cells, a subset highly enriched for hematopoietic progenitors, colony formation was inhibited at both disease stages, whereas CFU-GM colony formation derived from normal CD34+ cells was not affected by exposure to c-myb antisense oligodeoxynucleotides. These data suggest that CML chronic phase and blast crisis progenitors are both sensitive to the inhibitory effects of c-myb antisense oligomers, and that the lack of inhibition in partially purified CML-chronic phase progenitors is probably due to inefficient penetration of oligodeoxynucleotides into the clonogenic cells. The preferential effect of c-myb antisense oligodeoxynucleotides on colonies arising from the compartment that includes CML-CD34+ progenitors likely reflects the expansion of a cell population with high proliferative potential and elevated c-myb mRNA levels. (author). 26 refs, 4 figs, 3 tabs