Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five cases of acute myelogenous leukemia with massive mast cell infiltration in bone marrow and leukemic tumors of the soft tissue were examined to elucidate the relationship between leukemic cells and mast cells. Leukemic cells in each case showed no basophil/mast cell features and differentiated to neutrophil-like cells in liquid culture. Isolated mast cells failed to proliferate with or without growth factors used irrespective of culture conditions. Mononuclear cell fraction obtained from all patients gave rise to relatively numerous mast cells in interphase culture using IL-3 but not in other culture systems. The simultaneous addition of leukemic cell membrane and IL-3 or delayed addition of leukemic cell membrane produced more numerous and mature mast cells in the upper layer of interphase culture using IL-3. However, addition of leukemic cell membrane alone failed to increase the number of mast cells. Similar results were obtain using mononuclear cells obtained from volunteers and cord blood cells. These results indicate that a cell to cell contact or interstitial substance together with IL-3 are essential requirements for growth and maturation of mast cell precursors and that the cell membrane itself in some cases of leukemia has the ability to induce maturation of mast cell precursors.
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PMID:Leukemic cell membrane from acute myelogenous leukemias with massive mast cell infiltration has a mast cell differentiation activity under culture condition containing interleukin 3. 793 32

To determine whether a requirement for exogenous growth factors (GFs) for survival and proliferation could identify cases of AML which would respond best to GFs, singly and in combination, primary AML bone marrow samples were grown in suspension. Samples were classified as GF-dependent (61%), or GF-independent (39%) based on maintenance of Ki67+ cell number (proliferating cells) in the absence of exogenous GFs. GF-dependent samples had significant proliferative responses to steel factor (SF), GM-CSF and IL-3; mean Ki67+ cell number increased by 4.1-, 3.3-, and 5.2-fold, respectively. Significant stimulation was not seen for GF-independent cases; several were inhibited by exogenous GFs. SF was additive or synergistic with GM-CSF or IL-3 among GF-dependent cases; however, combinations were no more effective than single cytokines among the GF-independent group. GM-CSF plus IL-3 or the hybrid protein PIXY 321 did not increase the mean Ki67 ratio compared to the individual cytokines for any population. Flow cytometric determination of GF receptor expression was less predictive of GF response than was survival and proliferation in the absence of GFs. Suspension cultures in the absence of GFs can select patients most likely to benefit from therapeutic strategies using GFs for cell cycle recruitment.
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PMID:Identification of growth factor-responsive acute myelogenous leukemia based on factor-dependence for survival and proliferation. 796 31

In view of cellular immunotherapy with cytotoxic monocytes in minimal residual leukemia we have studied the effects of monocytes on the growth and survival of leukemic cells from cell lines and from patients with acute myeloid leukemia (AML). Using highly purified and interferon-gamma (IFN gamma) activated human monocytes, monocyte-mediated cytotoxicity (MMC) was evaluated in an MTT-based colorimetric cytotoxicity assay against six human leukemic cell lines (U937, THP1, KG1, K562, HL60, and 1,25(OH)2D3 differentiated HL60 cells) and cells from AML patients. Leukemic cells from cell lines with an immature phenotype were found to be resistant to MMC, whereas leukemic cells with a more mature and monocytic phenotype were sensitive. This paralleled the sensitivity to tumor necrosis factor-alpha (TNF-alpha). AML cells from patients with an immature phenotype (FAB-M1/M5A) were significantly less sensitive to MMC as compared to more mature AML cells (FAB-M2/M4/M5B). The growth stimulatory effects of non-activated monocytes on immature AML cells could be abrogated in the presence of IFN gamma or IL-3 and GM-CSF. In addition, these cytokines further potentiated MMC, preferentially affecting cells with a more mature phenotype. AML cells with an immunologically immature phenotype (CD34(high), HLA-Dr(low), CD13(low), CD14(low)) were revealed as the least sensitive cells to MMC. The growth stimulatory effects of IL-3/GM-CSF with or without TNF-alpha on AML cells correlated with resistance to MMC. In addition, the cytolytic effects of TNF-alpha in the presence of IFN gamma correlated with an increased susceptibility of AML cells to MMC. In conclusion, our data strongly indicate that MMC is related to maturation in AML, which is correlated to the differential stimulatory and cytolytic effects of monocyte-derived cytokines such as IL-3, GM-CSF, and TNF-alpha.
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PMID:Maturation-dependent susceptibility to monocyte-mediated cytotoxicity in acute myeloid leukemia. 805 79

We performed a phase I/II study of recombinant human interleukin-3 (rhIL-3) in 21 patients with aplastic anemia (AA) or myelodysplasia (MDS). Patients received 21-day cycles of IL-3 (0.5, 1.25, 2.5, 5.0, or 10 micrograms/kg/d) by subcutaneous injection followed by a 10- to 14-day washout period. Nineteen patients completed at least one 21-day cycle of IL-3. Frequent toxicities of IL-3 included headache, low-grade fever, and erythema at the injection site; at higher doses, weight gain and peripheral edema was seen. Eleven patients developed eosinophilia. Of the 20 evaluable patients, eight had increases in absolute neutrophil counts (seven with MDS, one with AA) including six of the nine patients receiving > or = 5.0 micrograms/kg/d. One AA patient became transfusion-independent for 8 months, while another AA patient had decreased transfusion requirements. Three patients with MDS had at least a doubling of their platelet count, and another patient experienced a 1.9-fold increase. One patient with RAEB progressed to aleukemic AML by the end of one treatment cycle. IL-3 was well-tolerated, but multilineage effects were seen in only 25% of patients with primary bone marrow failure states (five of 20 evaluable) and more commonly in patients with myelodysplastic syndromes. Its optimal use may be as part of combination hematopoietic growth factor therapy.
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PMID:A phase I/II study of interleukin-3 in patients with aplastic anemia and myelodysplasia. 806 86

A new strategy in the treatment of acute myelogenous leukemia is to attempt to increase the growth fraction of clonal leukemic cells prior to administration of chemotherapeutic agents by the administration of hematopoietic growth factors. We have studied the effect of GM-CSF on the cell cycle status and Ki67 nuclear antigen expression of AML blasts in vitro. The effect of growth factors and stromal cell co-culture on Ki67 expression in leukemic cell lines was also examined. Neither stromal cell co-culture nor exposure of factor-dependent and factor-independent cell lines to GM-CSF, IL-3, SCF, or combinations thereof significantly changed the percentage of cells expressing Ki67. In the AML population analyzed as a whole, exposure of blasts to GM-CSF for up to 96 h did not significantly change the percentage of cells in S phase or expressing Ki67.
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PMID:Effects of GM-CSF on Ki67 expression and cell cycle traverse in acute myelogenous leukemia specimens and cell lines. 806 62

The effects of leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) on blast progenitors from acute myeloblastic leukemia (AML) were examined using a blast colony assay in a serum-free culture system. LIF and IL-6 stimulated colony growth in 2 and 5, respectively, of 11 cases studied. The simultaneous addition of LIF with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3) or IL-6 produced a statistically significant increase of colony numbers in 3, 6 and 7 of 11 cases, respectively. Numbers of colonies increased significantly when IL-6 was added simultaneously with GM-CSF or IL-3 in 5 and 4 of 11 cases, respectively. LIF or IL-6 used in the primary culture did not significantly change the numbers of secondary colonies compared to GM-CSF. Previous exposure to LIF and IL-6 did not alter cellular phenotype or morphology, indicating that LIF and IL-6 did not induce the differentiation of fresh AML blasts.
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PMID:The effects of leukemia inhibitory factor and interleukin 6 on the growth of acute myeloid leukemia cells. 809 66

The 5 q deletion is frequently found in myelodysplastic syndromes and acute non lymphoid leukemia, but this anomaly is usually found in secondary diseases and associated with many other chromosomal aberrations. This report describes four cases of "de novo" acute leukemia with a sole 5q- anomaly. They had no cytological, genetic or clinical characteristics of secondary disorders. It is important to note that of the four patients studied, three had proliferation of immature blast cells. One case was classified as a MO AML and two as "undifferentiated" acute leukemia. Furthermore, these four cases of acute leukemia showed a deletion of the same portion of the long arm of chromosome 5: q22q33. On the same part of this chromosome many hematopoietic growth factor genes have been located, like IL3 and GM-CSF which have early undifferentiated hematopoietic stem cells as a their target.
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PMID:De novo acute leukemia with a sole 5q-: morphological, immunological, and clinical correlations. 812 11

To develop a model in which growth factor dependent human acute myeloid leukemia (AML) cells could be reliably engrafted onto murine recipients, the IL-3 or GM-CSF dependent human leukemic cell lines MO7E and TF-1 were engineered by infection with recombinant retroviruses to produce one of these factors. Retrovirally-infected, factor-producing MO7E or TF-1 cells became factor independent in culture while cells infected with a control (neo(r)) retrovirus did not. When these cells were injected intravenously into immunosuppressed Balb/C-nu/nu mice, human CD45+ cells were detected in the marrow of all 30 mice receiving hIL-3 or hGM-CSF-producing cells, but in 0/36 mice injected with uninfected or neo(r) virus-infected MO7E or TF-1 cells. Leukemic cell dissemination in mice injected with factor-producing MO7E cells progressed to cause hind limb paralysis in all animals by 7-12 weeks, and to involve the spleen and peripheral blood in 10/18 and 9/18 mice respectively. Injection of factor-producing TF-1 cells resulted in posterior thoracic tumor masses in all 12 mice by 5-11 weeks, while the spleen and blood were involved in six of those same animals. Southern analysis of retroviral integration sites demonstrated that the polyclonal nature of cells injected into mice was retained in the cells recovered from the same animals. When mice were injected with neo(r) virus-infected MO7E cells followed by 6 micrograms hIL-3 q/2 days i.p. all six mice showed hind limb paralysis and bone marrow involvement with a polyclonal population of MO7E cells by 8-13 weeks post injection. Thus, factor-dependent human AML cell lines will engraft in immunosuppressed, athymic nu/nu mice and disseminate with a pattern resembling human leukemia when provided with a source of the human factor(s) on which their growth is dependent in vitro.
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PMID:Cytokine-dependent engraftment of human myeloid leukemic cell lines in immunosuppressed nude mice. 818 43

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all-trans retinoic acid 10(-6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease.
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PMID:Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells. 819 61

For the optimal growth of clonogenic cells in acute myeloblastic leukemia (AML), several cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 are required in addition to colony-stimulating factor (CSF), which may be produced by blast cells themselves. In the present study, we addressed the potential role of endogenous production of TNF-alpha and/or IL-1 in the in vitro growth of AML clonogenic cells supported by IL-3. Addition of a specific neutralizing antibody against TNF-alpha (anti-TNF-alpha) to the culture significantly reduced the growth-stimulating effect of IL-3 on the cells in 11 of 14 patients. Simultaneous addition of anti-IL-1 alpha and anti-IL-1 beta also partly affected the growth, although to a much lesser extent when compared to the effect observed with anti-TNF-alpha. In 3 patients, the growth-stimulating effect of IL-3 was completely abrogated by anti-TNF-alpha or a combination of all three antibodies. Constitutive TNF-alpha transcript was observed in 5 patients and TNF-alpha protein was present in culture supernatant. Following in vitro culture, a transient but profound increase in c-fos, c-jun, TNF-alpha and IL-1 beta mRNA levels was observed. Anti-TNF-alpha inhibited the accumulation of TNF-alpha transcript, suggesting that membrane-integrated TNF-alpha may be partly responsible for the induction of TNF-alpha mRNA. It seems likely that the accumulation of these genes occurs through a protein kinase C-independent signaling pathway.
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PMID:Growth potentiating activity of endogenous production of interleukin-1 and tumor necrosis factor alpha in blast cells of acute myeloblastic leukemia. 831 77


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