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)

Acute mixed lineage leukemias (MLL) are a heterogeneous group of acute leukemias that express morphologic and/or immunophenotypic features of more than one hematopoietic cell line. The ontogenetic significance of this mixed lineage expression is unclear. We therefore studied the conviction of the lineage commitment in a group of MLL by examining the in-vitro response of five CD2+ (E-rosette receptor) acute myelogenous leukemia (AML) to a panel of proliferation and differentiation-inducing agents. Three of the five CD2+ AML were TdT-positive. Antigen receptor gene studies revealed no rearrangements at either the T beta or immunoglobulin heavy chain gene loci in any case. When blast-enriched cell populations were placed in short term suspension cultures with PHA, IL-2, PHA + IL-2, GM-CSF or TPA, three of the leukemias responded in a similar fashion while the remaining two cases showed no response. In the three MLL that responded to the in-vitro culture manipulations, features indicative of differentiation along the monocytic lineage pathway were observed. This differentiation was not pronounced in the presence of the phorbol ester TPA, and was manifested by loss of CD2 and CD7 expression, continued expression of myeloid antigens, and the development by the blasts of morphologic and cytochemical characteristics of monocytic cells. None of the five MLL showed any evidence of induced maturation along the T-lymphocyte line of differentiation with any of the agents used. rGM-CSF was the only exogenously added agent to induce proliferation; the proliferative response was slight and was seen in only one of the five leukemias. Therefore, the phenotypic expression of CD2 and CD7 in blasts from MLL is not indicative of irreversible commitment to T-lymphocyte development. The in-vitro loss of T-cell antigens in concert with the development of monocytic features in three of the five CD2+ AML in this study suggests the leukemic cells were preferentially committed to a non-lymphoid lineage differentiation pathway.
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PMID:The in-vitro response of CD2-positive acute myelogenous leukemia to proliferation and differentiation inducing agents. 169 68

A strictly factor-dependent cell line (UCSD/AML1) was established from a patient with the syndrome of multilineage acute leukemia with high platelets. The patient's cells and the cell line karyotype were 45,XX,-7,t(3;3)(q21;q26), typical of the syndrome of acute leukemia with high platelets. The cell line expresses CD34, CD7, TdT, and myeloid (CD13, CD14, CD33) and megakaryocyte/platelet (CD36, CD41, CD42b, CDw49b) antigens. In short-term culture, UCSD/AML1 cells proliferate in response to interleukin-3 (IL-3), IL-4, IL-6, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage CSF (GM-CSF), but not IL-1, IL-2, IL-5, or G-CSF. In long-term culture, proliferation can be sustained by GM-CSF, IL-6, or M-CSF. When maintained in GM-CSF, a small percentage of cells form multinucleated megakaryocyte-like giant cells. Culture with GM-CSF combined with IL-6, but not with IL-6 alone, increased giant cell formation fourfold to sevenfold. IL-6 alone or in combination with GM-CSF increased expression of platelet-related antigens. In contrast, culture with phorbol ester induced formation of macrophage-like cells. UCSD/AML1 is the first human acute nonlymphocytic leukemia cell line established from a patient with an acute leukemia syndrome associated with a specific chromosome abnormality.
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PMID:Characterization of a factor-dependent acute leukemia cell line with translocation (3;3)(q21;q26). 169 79

Tumor necrosis factor (TNF) inhibits granulocyte-colony-stimulating factor (G-CSF)-induced human acute myeloid leukemia (AML) growth in vitro. Incubation of blasts from three patients with AML in serum-free medium with TNF (10(3) U/ml), and subsequent binding studies using 125I-G-CSF reveal that TNF downregulates the numbers of G-CSF receptors by approximately 70%. G-CSF receptor numbers on purified blood granulocytes are also downmodulated by TNF. Downregulation of G-CSF receptor expression becomes evident within 10 min after incubation of the cells with TNF at 37 degrees C and is not associated with an apparent change of the dissociation constant (Kd). The TNF effect does not occur at 0 degrees C and cannot be induced by IL-2, IL-6, or GM-CSF. TNF probably exerts its effect through activation of protein kinase C (PKC) as the TNF effect on G-CSF receptor levels can be mimicked by 12-O-tetradecanoylphorbol-13- acetate. The PKC inhibitor Staurosporine (Sigma Chemical Co., St. Louis, MO) as well as protease inhibitors can completely prevent G-CSF receptor downmodulation. Thus, it appears TNF may act as a regulator of G-CSF receptor expression in myeloid cells and shut off G-CSF dependent hematopoiesis. The regulatory ability of TNF may explain the antagonism between TNF and G-CSF stimulation.
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PMID:Tumor necrosis factor downregulates granulocyte-colony-stimulating factor receptor expression on human acute myeloid leukemia cells and granulocytes. 170 66

High-dose recombinant interleukin-2 (rIL-2) therapy can induce long-term remission in patients with melanoma and renal and colon cancer. More recently, in vivo IL-2 therapy was shown to induce complete or partial remission in some cases of relapsed chemotherapy-resistant acute myeloid leukemia. We have investigated the phenotypic modifications of bone marrow cells obtained from five patients with acute myeloid leukemia in relapse receiving high-dose i.v. rIL-2. We found that, in three of five patients, IL-2 could induce, in vivo, an increase in the expression of CD54/ICAM-1 and to a lesser extent of CD58/LFA-3 on bone marrow leukemic blasts. This demonstrates that rIL-2 modifies directly or indirectly the expression of the cell surface molecules of the tumor cells themselves. Upregulation of such adhesion molecules could account for the enhancement of cell interactions between the tumor and effector cells such as T, natural killer, and phagocytic cells as well as being indicators of differentiation signaling.
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PMID:Cell surface expression of ICAM-1 (CD54) and LFA-3 (CD58), two adhesion molecules, is up-regulated on bone marrow leukemic blasts after in vivo administration of high-dose recombinant interleukin-2. 172 5

Three anti K562 monoclonal antibodies (MAb) 4.3, 4.6 and 4.8 reacting predominantly with cells of myeloid lineage, were tested for antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). MAb 4.6 (IgG3k) effectively mediated ADCC against K562 cells and fresh leukemic targets with effectors from healthy donors. However, for ADCC on chronic myeloid leukemia (CML) targets, effectors from CML patients in remission needed modulation with IL-2. All MAb showed significant CDC against peripheral blood (PB) and bone marrow (BM) cells obtained from CML patients in chronic phase, and untreated acute myeloid leukemia (AML) patients. MAb displayed no CDC against PB and BM cells from CML patients in remission and BM cells of Hodgkin's Disease (HD) patients with normal BM cellularity. In clonogenic assay, colony forming units (CFU) in the BM aspirate obtained from CML patients in chronic phase were significantly reduced by treatment with MAb and complement.
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PMID:Antibody dependent cellular cytotoxicity and complement mediated cytotoxicity on leukemic cells mediated by anti K562 monoclonal antibodies. 196 90

We investigated the induction of tissue factor by lymphokines in human monoblastic leukemia cell lines (U937) and leukemic cells from AML (acute myelogenous leukemia) patients. After incubation for 24 h, IL-2 enhanced the intracellular tissue factor 15-fold with U937 cells, and GM-CSF enhanced it 6-fold. In contrast, other lymphokines, such as IL-1-alpha, IL-1-beta, IL-3, IL-4 and G-CSF, did not affect the activity of tissue factor. The leukemic blasts, depleted of T-lymphocytes, taken from five out of 16 AML patients showed a 2.5-14-fold increase in the activity of tissue factor per cell following incubation with 200 u/ml of IL-2 for 72 h. The IL-2 induced tissue factor activity more markedly than GM-CSF. Tissue factor stimulation by IL-2 did not correlate with the expression of the IL-2 receptor, Tac, but correlated well with FAB classification of AML cells. IL-2 responders were found in M4 and M5 subtypes only, but not all M4/M5 leukemias responded to IL-2. These findings indicate that IL-2 can mediate the tissue factor induction in the monocytic type of AML and the effect is not mediated by Tac receptors. This may shed a new light on our understanding of hypercoagulability in acute monoblastic leukemia.
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PMID:Induction of tissue factor by interleukin-2 in acute myelogenous leukemia (AML) cells. 208 39

We recently described an IL-1 inhibitor found in urine of febrile patients. It is a 26-kDa glycoprotein that acts by blocking the binding of IL-1 to its receptor. In a search for a cell source for the urinary IL-1 inhibitor, we tested three promyelocytic cell lines, H-161, AML-193, and HL-60, for their ability to produce this protein. Under normal culture conditions none of these cell lines produce detectable IL-1 inhibitory activity. The H-161 cells were treated with differentiation-inducing agents, i.e., sodium butyrate, hemin, retinoic acid, DMSO, vitamin D3, and PMA alone or in combination with IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-gamma, granulocyte-CSF, macrophage-CSF, granulocyte/macrophage-CSF (GM-CSF), and Con A and tested for the production of IL-1 inhibitor. Production of IL-1 inhibitor was detected in cell supernatant, when H-161 cells were differentiated to adherent macrophage-like cells under the influence of PMA followed by a second signal provided by GM-CSF. Treatment of the other two cell lines, AML-193 and HL-60, with PMA plus GM-CSF also yielded similar IL-1 inhibitor protein. Partial purified H-161-derived IL-1 inhibitor showed specific binding to IL-1R-bearing cells and blocked the binding of IL-1 to its receptor and is thus similar to the urinary-derived molecule. We conclude the GM-CSF provides a signal to adherent macrophage-like cells to become "inhibitory macrophages" and to produce a competitive inhibitor of IL-1.
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PMID:Human granulocyte-macrophage colony-stimulating factor plus phorbol myristate acetate stimulate a promyelocytic cell line to produce an IL-1 inhibitor. 214 81

The in vitro incubation of NK cells with the lymphokine IL-2 stimulates the development of a population of activated cytotoxic lymphocytes (LAK cells). These activated cells have the capacity to recognize and kill a wide range of neoplastic cells. The cytotoxic activity of LAK cells does not appear to be directed against normal, non-neoplastic cells and we have recently examined the potential for using LAK cells as a method of purging bone marrow for autologous transplantation in patients with widespread neoplastic diseases. We have utilized an experimental system consisting of the incubation of LAK cells from inbred F344 rats and normal bone marrow and demonstrated that this procedure does not interfere with the ability of the treated bone marrow to reconstitute lethally-conditioned recipients. The frequency and rate of reconstitution is the same in treatment and control groups, including incubation periods that extend up to 18 hours. When RNK-16 leukemia cell line (a spontaneous large granular lymphocyte leukemia that is syngeneic to the F344 strain) is added to the incubation mixture, the LAK cells have the ability in vitro to recognize the neoplastic cells and prevent the transmission of the leukemia to naive animals following bone marrow transplantation. As expected from the in vitro LAK cytotoxic activity, these activated cells are capable of recognizing and eliminating a variety of neoplasms. To date we have tested three different hematopoietic tumor lines derived from the F344 strain and one that was induced in an unrelated BN strain. In each case, the F344 LAK cells demonstrated an ability to prevent the transmission of a fatal leukemia and significantly prolong the survival of animals that had received larger numbers of neoplastic cells. The tumor lines examined included the RNK-16 line (NK cells), the Dunning leukemia (monocyte-lymphoblastic leukemia), a T-lymphocyte lymphoma and the acute myelogenous leukemia of BN rats (BN AML). Comparison of the results of these purging experiments to those seen when control animals are injected with graded doses of the individual tumors indicate that the LAK cells are eliminating approximately 2-3 logs of neoplastic cells. The ability of LAK cells to kill a wide range of tumors without damage to the ability of the recipient stem cells to reconstitute the bone marrow may allow for an important application for this type of purging technique in patients with neoplasms for which specific immunological or chemical therapies do not exist.
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PMID:Lymphokine-activated killer (LAK) cell purging of bone marrow. 230 77

We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70-75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody (MoAb), designated Mik-beta 1, which has been recently developed. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis. These results indicate that flow cytometric analysis using MoAbs, anti-Tac, and Mik-beta 1 is useful for detecting the expression of the IL-2R chains.
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PMID:Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells. 238 56

A 34-year-old male patient developed an isolated pericardial relapse of an acute myelogenous leukemia (M3) 11 months after marrow grafting from his HLA-identical brother. Alloenzyme pattern analysis revealed recipient type of the myeloblasts obtained from the pericardial effusion. Recurrence of the original leukemia was preceded by a reactivation of latent cytomegalovirus (CMV) infection which, in spite of a systemic humoral immune response to the virus, persisted in the pericardium as shown by dot-blot hybridization using CMV-specific DNA fragments. Activated T cells propagated with IL-2 from the pericardial effusion did not reveal any cytotoxic or restimulation capacity on the original or relapse myeloblasts, nor on other donor, recipient or NK target cells. Local coincidence of virus persistence and leukemic relapse suggested CMV-mediated modulation of the immune response in the pericardium with consequent induction of a proliferation of the original malignant cell clone. After local chemotherapy and one course of systemic treatment the patient is still in complete remission--longer than after the marrow grafting.
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PMID:Isolated pericardial relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia. 254 72


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