Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-eight consecutive patients with a FAB-classified primary myelodysplastic syndrome (MDS) were investigated for in vitro growth of colony-forming units for granulocyte-macrophage precursors (CFU-GM) and cytogenetic analysis of bone marrow cells. Abnormal CFU-GM growth was found in 30 patients (79%), and clonal chromosome abnormalities were found in 13 patients (34%). The eight patients who showed normal CFU-GM growth were either cytogenetically normal (n = 5), or had a 5q-deletion (n = 3) as single or dominating karyotypic abnormality. Among the 30 patients with reduced or no colony growth, ten patients had a clonal chromosome abnormality. Leukemia developed in eight patients. None of them grew any CFU-GM colonies, and three of them were cytogenetically abnormal at the time of diagnosis of MDS. Analysis of the bone marrow in vitro growth for CFU-GM and the karyotype in patients with MDS emphasizes the close relationship between these disorders and manifest acute leukemia. Subgroups of MDS may be defined by a cytogenetic classification (e.g., the 5q-syndrome), and the CFU-GM growth pattern can be of value for predicting leukemic transformation.
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PMID:Bone marrow in vitro growth and cytogenetic studies in patients with FAB-classified primary myelodysplastic syndromes. 236 12

Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.
Leukemia 1990 Apr
PMID:Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia. 236 84

We investigated the effects of interleukin-7 (IL-7), a stromal cell derived cytokine known to stimulate proliferation of murine lymphoid precursor cells, alone and in combination with IL-3, IL-1, and IL-6 on proliferation of purified blast cells in acute lymphoblastic leukemia (ALL). After 7 days of liquid culture DNA-synthesis was induced in six of 10 cALL, three of five B-ALL, and two of seven T-ALL samples by IL-7 or IL-3 or both. Monitoring of leukemic cell populations in suspension culture by Southern blot analysis of immunoglobulin and T cell receptor gene rearrangements revealed preferential stimulation of the leukemic cell clone by both IL-7 or IL-3 in one cALL and one B-ALL sample. In these cases the combination of IL-7, IL-3, and IL-1 was as effective in stimulation of DNA-synthesis as the most potent cytokine alone. There was no evidence of lymphoid maturation during liquid culture as defined by immunophenotyping using flow cytometry. Stimulation of nonleukemic cell population seen in two other cases of cALL was associated with residual erythroid and granulocyte-macrophage colony forming cells after liquid culture as defined in parallel clonogenic assays in one and detection of CD 33+ and CD 13+ cells after culture in the other cALL sample. We conclude that IL-7 directly stimulates monoclonal growth of leukemic cells in a subset of ALL without evidence of concurrent maturation induction.
Leukemia 1990 Aug
PMID:Effects of recombinant human IL-7 on blast cell proliferation in acute lymphoblastic leukemia. 238 82

The possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
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PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48

We established and maintained long-term cultures of marrow from normal dogs and dogs with lymphoma or leukemia by single inoculations of mononuclear cell suspensions. Media containing only horse sera (as opposed to horse and fetal calf sera) and catalase (for antioxidative effect) supported improved culture viability, as indicated by increased recovery of progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) and the release of abundant erythroid cells in the cultures for up to 3 weeks. CFU-GM were maintained for at least 3-4 weeks of culture. Culture appearance, cell counts, and assays of CFU-GM were used to compare the culture kinetics of tumor-involved marrow to normal marrow specimens. Cultures of marrow with extensive tumor involvement tended to be less viable, apparently due to a relative lack of competent progenitors. To investigate whether canine long-term marrow culture provided a purging effect similar to the loss of tumor cells noted in human long-term cultures of marrow from patients with chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML), we established long-term marrow cultures from 28 dogs with histologically confirmed untreated lymphoma or leukemia. Eleven of these dogs had cytogenetically marked tumor cells in the marrow at the initiation of culture. In six dogs with lymphoma and one dog with acute monocytic leukemia (AMoL) French-American-British classification (FAB) M4 leukemia, we could detect no cytogenetic evidence for persistence of the tumor clones in individually plucked or pooled CFU-GM grown from 3-week-old long-term cultures. In one case of AML (FAB M2), 80% of CFU-GM recovered from long-term cultures at 4 weeks still contained an extra metacentric marker chromosome associated with the continued presence of the leukemic clone in the cultures. Our documentation of a purging effect for some tumors supports the use of this canine model system in the investigation of autologous marrow transplantation with long-term cultured cells for humans with lymphoma and leukemia.
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PMID:Long-term culture of canine marrow: cytogenetic evaluation of purging of lymphoma and leukemia. 239 54

We have studied peripheral blood blast cells from a patient with acute myeloblastic leukemia (AML) whose cells proliferated autonomously at high cell density, but only in the presence of adherent cells. At low cell density in suspension culture and in a clonogenic assay, blast cell growth was stimulated by recombinant granulocyte macrophage colony stimulating factor (GM-CSF) and recombinant interleukin-1 (IL-1) independently. The response to rIL-1 was inhibited (less than 90%) by anti-GM-CSF, suggesting that the proliferative response to IL-1 was mediated by GM-CSF. This was supported by experiments which demonstrated that blast cell conditioned medium prepared in the presence of IL-1 contained GM-CSF activity which stimulated the growth of normal granulocyte-macrophage precursors (CFU-GM) and of homologous GM-CSF responsive AML blasts. As IL-1 but no GM-CSF activity was detected in BCCM prepared without exogenous IL-1 and a neutralizing antibody to IL-1 inhibited the autonomous growth of blasts in suspension culture, we conclude that the endogenous secretion of IL-1 by leukemic cells stimulated autocrine GM-CSF secretion, inducing autonomous growth of the blast cell population.
Leukemia 1990 Jan
PMID:Endogenous interleukin-1 can regulate the autonomous growth of the blast cells of acute myeloblastic leukemia by inducing autocrine secretion of GM-CSF. 240 62

This report describes the characterization and expression of a human myeloid differentiation antigen defined by use of an IgG1 monoclonal antibody (AHN-7). This antibody binds to many granulocytic precursors in normal marrow, to most but not all granulocyte-macrophage progenitors (CFU-GM), and to approximately half of nonlymphoid leukemia specimens. The protein antigens recognized by AHN-7 were purified from 35S-labelled HL-60 cells by antibody affinity column chromatography. The molecule reacting with AHN-7 was markedly heterogeneous, appearing as several forms ranging in pl from 4.5 to 6.4 with apparent molecular weights from 43,000 to 68,000. The molecules were not disulfide-linked. Proteins bearing the antigen were minor components of the plasma membrane. The antigen was expressed by normal human peripheral blood neutrophils, monocytes, eosinophils, and basophils, and weakly on a small percentage of lymphocytes; it was not detected in red blood cells, platelets, or the majority of lymphocytes. The antibody also bound to a variety of human myeloid leukemia cell lines but not to any lymphoid leukemia cell line tested. AHN-7 had no effect on several in vitro neutrophil functions tested.
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PMID:Identification and purification of the human myeloid differentiation antigen recognized by monoclonal antibody AHN-7. 243 75

In vitro and in vivo studies were conducted to obtain basic information on the activity of gamma interferon (IFN-gamma) in acute myelogenous leukemia (AML). In a selected case of AML, recombinant IFN-gamma, but not IFN-alpha, induced differentiation of primary leukemic blasts in vitro. Similarly, IFN-gamma inhibited leukemic colony formation in vitro. This contrasted with IFN-alpha which was inactive. In one case of AML (M2), partially purified IFN-gamma given intravenously caused a shift of the WBC profile from immature blasts to maturing myeloid cells and neutrophil granulocytes. Intravenous IFN-gamma treatment of another patient who had AML as a second malignancy resulted in a complete hematologic remission, normalization of marrow granulocyte-macrophage colony-forming cell in vitro growth, and conversion of marrow cytogenetics from 95% hyperdiploid clone with complex abnormalities into 100% diploid. The results indicate a potential use of IFN-gamma in the treatment of selected patients with AML and the possibility of in vitro pretreatment evaluation of these patients' leukemic response to IFNs.
Leukemia 1987 Jan
PMID:Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon. 244 29

The in vitro actions of leukemia inhibitory factor (LIF) purified from Krebs tumor conditioned medium, were analyzed on murine leukemic M1 and WEHI-3B D+ cells and on normal hemopoietic progenitor cells. LIF has no observable effects on WEHI-3B D+ cells but rapidly induced macrophage differentiation and loss of clonogenicity in M1 cells, resulting in the formation of abortive clones or differentiating colonies of reduced size and number. These effects were observable within one to two cell divisions in the presence of LIF and were irreversible. Addition of macrophage-colony-stimulating factor (CSF) but not granulocyte/macrophage-CSF, granulocyte-CSF, or multi-CSF reduced the LIF-induced suppression of colony numbers and size. G-CSF had a slower differentiation-inducing action on M1 cells than LIF but potentiated the differentiation-inducing effects of low concentrations of LIF. LIF had no colony-stimulating activity for normal granulocyte-macrophage progenitor cells and did not alter their quantitative responsiveness to CSF. However, culture of normal progenitor cells in the presence of LIF, but initial absence of CSF, reduced the survival of these cells. The differing actions of LIF and G-CSF on M1 leukemic cells suggest the existence of distinct mechanisms for inducing macrophage differentiation in these leukemic cells.
Leukemia 1988 Apr
PMID:Clonal analysis of the actions of the murine leukemia inhibitory factor on leukemic and normal murine hemopoietic cells. 245 26

The effects of human recombinant granulocyte and granulocyte-macrophage- (G- and GM-CSF), and of purified macrophage-stimulating factors (CSF-1), were tested on populations of leukemia cells isolated from 18 patients with different types of acute myeloid leukemia. Cell proliferation and differentiation were studied by culturing the cells in suspension for 7 days in the presence of CSF or medium alone. Spontaneous cell proliferation, as assessed by tritiated thymidine uptake, was observed in 9 of the 18 cases. GM-CSF induced proliferation in seven of the nine cases without spontaneous growth and increased spontaneous proliferation in nine cases. G-CSF added alone was also found to strongly stimulate leukemic blast cell proliferation, in which a translocation involving the long arm of chromosome 17 was observed. Low levels of CSF-1 stimulation were also observed in some cases. No clear morphological modification supporting evidence of terminal differentiation was observed, whereas modulation of some cell surface antigens was detected by flow cytometry. Thus, most leukemia cells still depend on growth factors for their proliferation, GM-CSF appearing the most effective. On the other hand these factors were not able to induce terminal differentiation.
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PMID:Growth response of human myeloid leukemia cells to colony-stimulating factors. 245 72


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