Showing papers on "Myeloid published in 1972"

Normal differentiation of myeloid leukaemic cells induced by a differentiation-inducing protein.

Abstract: VARIOUS types of cells release an inducer for the formation of colonies in vitro with mature differentiated macrophages and granulocytes from single normal undifferentiated haematopoietic cells1–8. Using purified inducer from a cloned line of mouse fibroblasts, we have shown that this induction requires a protein (MGI) with a molecular weight of 65–70,000 and a low molecular weight co-factor, both secreted by the fibroblasts9. Adenine or adenine-containing nucleotides can substitute for the co-factor9,10. We have also shown that non-purified conditioned medium produced by human cells can induce undifferentiated cells from patients with acute myeloid leukaemia to differentiate into mature granulocytes11.

Lymphocyte cytotoxicity reactions to leukemia-associated antigens in identical twins.

Abstract: Cellular cytotoxicity reactions to human leukemia cells were measured with a sensitive, quantitative assay of cell-mediated immunity. Freshly explanted leukemia cells, rather than tissue culture cells, were tested to ensure that the antigens detected were not acquired in vitro. Identical twins, one member of each pair having leukemia, were used to minimize genetic variables and histocompatibility differences, thereby providing comparable normal cells to control for the leukemic cells. Leukemia-associated antigens were detected on the cells of seven of ten leukemic patients. In no instance was reactivity observed against only the cells of the normal twin. Lymphocytes from three identical twins, seven parents, two siblings and eight normal unrelated individuals were cytotoxic for cells from the leukemic patients but not for cells from these patients' normal identical twins. Lymphocytes from adults had a much higher incidence of reactivity (46%) against the leukemic cells than did the cells of children (9%). Positive lymphocyte cytotoxicity reactions to leukemia-associated antigens indicate previous sensitization which could have resulted from infection with an environmental agent such as a virus.

Competitive in vivo proliferation of foetal and adult haematopoietic cells in lethally irradiated mice.

Abstract: The relative proliferative capacity of haematopoietic cell populations derived from 22-week-old adult bone marrow and 14–18 day foetal liver has been studied in lethally irradiated syngeneic recipients by means of chromosome markers. Although starting at a disadvantage in terms of the number of colony-forming units (stem cells) injected, the foetal liver-derived populations steadily increased their relative numbers in the myeloid and lymphoid tissues over a period of several weeks until a plateau was reached. It is suggested that stem cells in foetal liver have, on average, a higher intrinsic capacity for self-renewal than do those in bone marrow, and that this capacity falls to the adult level within about ten weeks of transfer.

Details of blood changes in 32 patients with pancytopenia associated with long-term exposure to benzene.

Abstract: Aksoy, M., Dincol, K., Erdem, S., Akgun, T., and Dincol, G. (1972).Brit. J. industr. Med.,29, 56-64. Details of blood changes in 32 patients with pancytopenia associated with long-term exposure to benzene. A study was performed on 32 pancytopenic patients who had had long-term exposure to benzene. They had been subjected to high concentrations of benzene varying from 150 to 650 p.p.m. for from 4 months to 15 years. Apart from four, in whom the platelet count was normal, all had pancytopenia. As the bone marrow punctures of the pancytopenic patients showed a great variation from acellularity to hypercellularity, the patients were classified and studied according to the bone marrow findings. Anaemia was macrocytic in 14, in three of whom a megaloblastic erythropoiesis was detected. The findings in some patients, such as mild reticulocytosis, hyperbilirubinaemia, erythroblastaemia, an increase in quantitative osmotic fragility and in faecal urobilinogen excretion as well as elevated serum LDH levels, suggested that these might be attributed to either increased haemolysis or the presence of ineffective erythropoiesis. The HbF content in 20 out of 24 pancytopenic patients was above normal, ranging between 3·2% and 19·5%, with a mean of 6·1%. Mean values of HbF in groups with a hypoplastic, hyperplastic, and normoplastic bone marrow were essentially the same. The absolute amounts of HbF exceeded 400 mg/100 ml in only 8 out of 24 patients, all of whom survived. The HbA2 level was within normal limits in 21 out of 24 pancytopenic patients. It was definitely decreased in one and slightly so in three. These findings may suggest that HbA2 occasionally shows a tendency to decrease in some patients with chronic benzene poisoning. The maturation arrest in both the myeloid and erythroid elements was the most frequently encountered finding. In the bone marrow examinations, gaint erythroid precursors varying from 9% to 72% were detected in two patients. In one of them, who also had hepatosplenomegaly, the development of preleukaemia was accepted. Varying mortality rates were estimated in the above-mentioned groups. The results obtained from treatment with steroids, androgens, phyto-haemagglutinin, and oxymetholone are also described.

The Correlation Between the Proliferative and the Cytotoxic Responses of Mouse Lymphocytes to Allogeneic Cells in Vitro

Abstract: The relationship between the antigen recognition phase (mixed lymphocyte culture) and the cytotoxic effector phase of a mouse allograft reaction in vitro has been studied. In addition, the responsiveness of thymus-derived (T) cell depleted and bone-marrow derived (B) cell enriched lymphocyte populations to alloantigens was investigated. Using CBA mouse spleen cells, there was a separation in time (48 hr) between the maximal proliferative response ( 3 H-thymidine uptake) and the peak generation of cytotoxic lymphocytes as measured by a 51 Cr release assay. Quantitation of the cytotoxic response obtained by using spleen cells of neonatal thymectomized (NnTx) mice or adult thymectomized lethally irradiated and bone marrow-protected (ATxBM) mice demonstrated that the cytotoxic allograft response may be useful as a functional test for residual mature T cells within a lymphocyte population. Spleen cells of congenitally athymic (“nude”) mice did not contain precursor cells of cytotoxic lymphocytes. However, they proliferated in the “one way” mixed lymphocyte culture as did spleen cells of NnTx or ATxBM mice. Evidence is given that the proliferation of nude spleen cells was due to dividing lymphocytes and not to contaminating erythroid or myeloid elements. It is concluded that in the mouse both B and T cells are capable of proliferation in vitro due to alloantigens. Whereas T cells differentiate into cytotoxic effector cells, B lymphocytes respond independently of helper cells (T lymphocytes) and the mitotic response may be part of a humoral response to alloantigens in vitro.

Characteristics of cell proliferation in acute leukemia.

Abstract: Bone marrow aspirates and venous blood samples from 26 subjects with acute leukemia in relapse and from 10 nonleukemic controls were incubated in vitro with tritiated thymidine and examined by autoradiography. Twenty leukemic patients were studied again during the course of chemotherapy. The number of labeled cells per 100 nonerythroid nucleated cells provided an estimate of the population, which was in the DNA-synthesis phase of the generative cycle. This ratio was used as an indicator of the size of the proliferative population of bone marrow. The fraction of proliferating cells was significantly smaller in the leukemic bone marrows during relapse than in the controls. In the leukemic subjects, the peripheral blood blasts showed a smaller ratio of proliferating cells than that in bone marrow, but this difference was statistically not significant. The 13 patients who eventually responded to chemotherapy showed a marked increase in the actively proliferating population in the bone marrow early in the course of therapy, whereas all those patients who failed to go into remission showed no early rise in the proliferating pool. This procedure may assist in the early detection of nonresponders to the cytocidal agents with which acute leukemia patients are being treated so that it may be possible to change the therapeutic approach before toxicity ensues.

Muramidase in myeloproliferative disorders terminating in acute leukemia.

Abstract: During serial studies of serum muramidase activity (SMA) over a 4-year period on 168 patients with leukemia and myeloproliferative disorders (MPD) eight patients—one with polycythemia vera (PCV), one with agnogenic myeloid metaplasia, three with atypical myeloid metaplasia, and three with chronic myelogenous leukemia—developed acute myeloblastic or acute myelomonocytic leukemia (AMML). Onset of leukemia occurred early during the course of the disease and was associated with striking elevation of SMA in all six patients with AMML. Three patients studied in detail had significant hypokalemia possibly related to toxic effects of an excess of muramidase on renal tubules. Seven of the eight patients received therapy, consisting of splenic irradiation, alkylating agents, or both. Rapid rise of SMA in patients with MPD may herald the onset of acute leukemic metamorphosis.

Characterization of a factor required for the differentiation of myeloid and lymphoid cells in vitro.

Abstract: The properties of a factor which is secreted by a cloned tumor cell line (JLS-V5) have been examined. The factor has been assayed in two culture systems. The factor induced the formation of colonies containing granulocytes and macrophages from mouse bone marrow cells cultured in a semi-solid agar medium. The factor also stimulated a normal primary immune response against erythrocyte antigens in immunologically unresponsive mouse spleen cultures. These spleen cultures were prepared from unimmunized mice in medium containing a deficient fetal bovine serum. The factor has been purified 500-fold from the serum-free culture supernatants of JLS-V5 cells. When the factor was treated with a variety of chemical and enzymatic reagents and then fractionated by gel filtration, the biologic activity for each culture assay resulted from the same molecular weight fractions. Acrylamide gel electrophoresis indicates the factor has a m.w. of 70,000 to 80,000.

Cytogenetic studies in myeloproliferative disorders.

Abstract: Cytogenetic studies of bone marrow preparations and/or whole blood cultures were carried out in 18 patients with myeloproliferative disorders. The Ph1 chromosome was detected in six of nine patients with chronic myeloid leukemia. Chromosomal abnormalities included: group C trisomy in a patient with myeloid metaplasia, and a 46 chromosome karyotype but with a missing D group and an extra C group chromosome in a patient with chronic monocytic leukemia.

Daunorubicin. Results in childhood leukaemia.

Abstract: Fifty children with acute leukaemia (44 lymphatic, 6 myeloid) were treated with daunorubicin. In 3 cases, it was given in courses of daily injections; in 47, single injections were given at 7- to 14-day intervals. On the latter (intermittent) regimen, in combination with prednisolone, a good response—complete, bone marrow, or clinical remission—occurred in 22 of 27 cases (81%) of `new9 or previously untreated acute lymphoblastic leukaemia but in only 3 of 13 cases previously treated with other drugs. With acute myeloid leukaemia a good response occurred only when daunorubicin was given in combination with other cytotoxic drugs. The major side-effect was bone marrow depression with the related complications of haemorrhage and infection. Cardiotoxicity was not a problem; the cumulative total dose of daunorubicin did not exceed 26·8 mg/kg. This study indicates that intermittent dosage with 2-3 mg/kg at intervals of 7 to 14 days is as effective as, and no more toxic than, the courses of daily injections that have been commonly used.

Assessment of the mixed leucocyte reaction by target cell death: a study of leukaemic cells

Abstract: In one way mixed cultures between normal and acute leukaemic cells, cytotoxic effect was assessed by the subsequent amount of isotope released from 51Cr labelled allogeneic target cells (Chang liver cells). Observations were made during the acute phases and, where possible, in remission. All cells used in these cultures were of known HL–A phenotype. Normal lymphocytes exhibited a variable response to leukaemic cells. In many cultures the increased cytotoxicity was greater than that found after mixed cultures of normal cells. This was not related to the number of circulating blast cells nor directly to HL–A differences between cells.