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

Plasma levels of soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8) and soluble intercellular adhesion molecule 1 (sICAM-1) were determined by ELISA assays in about 100 patients with hairy cell leukemia (HCL), acute myelomonocytic leukemia (AMMoL), acute myelocytic leukemia (AML), chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), acute lymphoblastic leukemia (ALL), adult T-cell leukemia (ATL), and mycosis fungoides (MF). Additionally, cultured AML, ALL, and CLL cells grown with and without 12-0-tetra-decanoyl-phorbol-13-acetate (TPA) were tested for IL-2R (CD25) expression by indirect immunofluorescence. Supernatants of these cultures were also tested for sIL-2R by ELISA. Elevated sIL-2R levels were found in HCL patients at initial diagnosis and relapse, in AMMoL, in AML, in the accelerated and non-accelerated phases of B-CLL, in PLL, in non-T/non-B ALL, in B-ALL in mixed lineage ALL, in T-CLL, in T-ALL, and in active MF. Reduced levels of sIL-2R were encountered in HCL patients in remission, in pre-T-ALL, and in MF patients in remission. Also, in non-accelerated CLL sIL-2R levels were less elevated than in later stages of the disease. In T-CLL, sIL-2R was only slightly elevated. Thus, we believe sIL-2R could prove to be a useful marker of disease stage, subtype, and prognosis in several hematologic malignancies. The cultures with and without TPA suggested that the undetermined source of sIL-2R in HCL, ALL and AML could indeed be the malignant cells but perhaps not so in the case of B-CLL. Plasma sCD8 was found to be below normal control levels in HCL, and lowest in relapsing cases. In addition, sCD8 levels were below normal in pre-T-ALL, and in MF. Levels in the non-accelerated phase of B-CLL approximated those of controls. Elevated levels of sCD8 were observed in AML, AMMoL, accelerated stage B-CLL, PLL, non-T/non-B ALL, B-ALL, mixed lineage ALL, T-ALL, T-CLL, and ATL. Thus, in a few instances, sCD8 may also correlate with disease subtype, as well as stage. Although sICAM-1 levels were elevated in all leukemias, its levels in CLL did not appear to be related to disease activity. Whether this is true or not for other leukemias would require additional work on sICAM-1 levels and its relationship to disease activity and prognosis.
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PMID:Soluble interleukin-2 receptor, soluble CD8 and soluble intercellular adhesion molecule-1 levels in hematologic malignancies. 790 67

The reconstitution of lymphocyte subsets after high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) was studied using two-color flow cytometry in 14 patients with acute leukemia (four AML and two ALL) and malignant lymphoma (six NHL and two HD). The CD3+HLA-DR+ lymphocytes (activated T cells) and CD8+ lymphocytes increased markedly by 4 weeks after PBSCT. Most of the increased CD8+ lymphocytes were CD11b-, S6F1+ cells and CD8+CD11b+ cells remained low throughout the follow-up period. The CD4+ lymphocytes remained below the normal range up to 34 weeks after PBSCT. The ratio of CD4+ to CD8+ lymphocytes (CD4/CD8 ratio) transiently increased and then decreased below 1.0 at 2 weeks after PBSCT. The CD19+ lymphocytes and the CD3-CD16+CD56+ lymphocytes returned to normal levels in the early period. The CD4+CD45RA+ lymphocytes (suppressor-inducer) decreased to below the normal range, while the CD4+CD45RO+ lymphocytes (helper-inducer) increased more rapidly than the CD4+CD45RA+ lymphocytes. This study shows that an immunosuppressed state exists after PBSCT as is seen after bone marrow transplantation (BMT) and that B cell reconstitution is more rapid in PBSCT than in BMT.
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PMID:Reconstitution of lymphocyte subsets after peripheral blood stem cell transplantation: two-color flow cytometric analysis. 791 3

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

A 59-year-old woman who had an 8-year history of acute myeloblastic leukemia (AML) developed granular lymphocytic leukemia (GLL). She had a small number of granular lymphocytes (GL) in her bone marrow (BM) at the onset of AML. The GL increased during complete remission (CR) of AML, but not at the relapse. During the third CR state of AML, GL increased to 4.0 x 10(9)/l in the peripheral blood (PB). The GL were T-cell receptor (TCR) alpha beta+ T cells and expressed both CD4 and CD8 antigens. Rearrangements of TCR beta and gamma chain genes were detected in the peripheral blood mononuclear cells (PBMNC), confirming that this patient had GLL. The PBMNC from the patient responded weakly to PHA or ConA, yet they responded to her own bone marrow mononuclear cells (BMMNC) or CD4-depleted BMMNC that contained AML cells stronger than her own PBMNC or normal PBMNC. These observations suggest that monoclonal proliferation of GL developed after the reactive proliferation of GL in response to AML cells.
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PMID:CD4+ CD8+ granular lymphocytic leukemia arising in a patient with acute myeloblastic leukemia. 796 33

The experiments have been undertaken whether DNA contents could be measured using whole blood lysis method by FACScan. Cell population in the phases of G1, S and G2 + M were well analyzed, when we used 3 x 10(6) cells lysed with 0.1% Triton X-100 in 1 ml of phosphate buffered saline, staining with 30 micrograms/ml of propidium iodide (PI) within 30 min after staining with PI. We have further developed cell cycle analysis for cells bearing lineage specific antigens recognized with FITC-conjugated monoclonal antibodies using two color analysis. When we fixed cells with 50% ice-cold ethanol after staining cells with FITC-conjugated antibodies, positive population ratio in these cells have been unchanged before and after fixing for CD3, CD4, CD5, CD8. CD10, CD19, CD14, CD33, and HLA-DR, but CD7 positive cells were markedly decreased after fixing. Using this method, CD41 positive leukemia cells have 3.4% in S phase and 6.8% in G2 + M phase, while CD41 negative cells have 1.8% in S phase and 2.0% in G2 + M phase in a patient with AML: M7, resulting leukemia cells were rich in S phase and G2 + M phase. The similar results were obtained in patients with AML:M2 using CD33 antibodies. During the clinical course, the changes of the blast numbers were well-correlated with changes of S-phase proportion in the patient with AML:M2. Among 47 patients with hematological malignancies in our hospital tested here, only 2 cases with 4.3% of total patients showed to have aneuploidy in malignant cells. One is a patient with non-Hodgkin lymphoma, the other is myelodysplastic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Analysis of DNA contents in hematological malignant cells using whole blood lysis method]. 799 13

The multidrug resistance-associated protein (MRP) gene is a member of the ATP-binding cassette transporter gene superfamily and may be partially responsible for clinical drug resistance. Reverse transcriptase-polymerase chain reaction was used to measure MRP mRNA in normal hematopoietic cells from bone marrow and peripheral blood as well as patients with high risk acute myelocytic leukemia and multiple myeloma. All normal peripheral blood cells, regardless of cell lineage (CD4, CD8, CD14, CD15, CD19, CD56), expressed a similar basal level of MRP mRNA. Specimens from bone marrow containing mixed lineages also expressed a similar basal level of MRP expression. In patients with acute myelocytic leukemia, 10 of 12 (83%) of the specimens had detectable MRP mRNA, but the level of expression was similar to that of normal blood cells and low compared to a cell line known to overexpress MRP (H69/AR). All myeloma patients (12 of 12) had detectable MRP mRNA expression at levels comparable to normal peripheral blood and bone marrow cells. We conclude that MRP is commonly expressed in normal hematopoietic cells as well as certain hematopoietic malignancies. The therapeutic relevance of MRP expression is unknown, but these studies emphasize the importance of measuring MRP expression in normal cells as a point of reference and comparison for detection in malignant cells. We also recommend obtaining sequential specimens from patients, which may reveal an increased expression of MRP from baseline as the disease progresses and becomes resistant.
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PMID:Analysis of multidrug resistance-associated protein (MRP) messenger RNA in normal and malignant hematopoietic cells. 806 63

We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL-2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients with chronic lymphocytic leukemia (CLL) and evaluated them in relation to clinical and biological parameters of the disease, as well as serum immunoglobulin E (IgE). Compared to 31 normal individuals, 42 CLL patients had increased levels of sCD23 (98.4 +/- 127.7 versus 0.9 +/- 0.3 U/ml, p < 0.001), sIL-2R (6080 +/- 7030 versus 1420 +/- 640 pg/ml, p < 0.001), sTfR (12,100 +/- 11,250 versus 5000 +/- 1050 ng/ml, p < 0.001), and sCD8 (510 +/- 191 versus 234 +/- 89 U/ml, p < 0.001), but normal sCD4 levels. Mean sCD23 levels remained normal in patients with non-Hodgkin's lymphoma (other than small lymphocytic), Hodgkin's disease, hairy cell leukemia, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), multiple myeloma, or solid tumors. Advancing Rai clinical stage was associated with a progressive elevation of sCD23 (p < 0.001), while sCD8 (p < 0.05), sIL-2R (p < 0.001), and sTfR (p < 0.005) were highest in stage 2 patients. Discriminant analysis confirmed the value of soluble receptor determinations in the clinical evaluation of CLL patients. sCD23 correlated with sIL-2R (p < 0.001) and sTfR (p < 0.05) but not with sCD4 or sCD8, and displayed an inverse relationship with serum IgE (NS) and total gamma-globulin (p < 0.05). sIL-2R correlated with sCD23 (p < 0.001), sTfR (p < 0.001), sCD4 (p < 0.01), and sCD8 (p < 0.01). The lymphocyte count correlated with serum lactate dehydrogenase (LDH) (p < 0.05), sCD23 (p < 0.001) and sIL-2R (p < 0.01) but not sTfR, sCD8, or sCD4. Chemotherapy produced consistent reductions of sCD23 levels in two responding patients. We conclude that: (i) sCD23 is considerably elevated in CLL, correlates with the tumor mass and clinical stage, and could be helpful in monitoring these patients; and (ii) sIL-2R, sCD8, and sTfR levels are less specifically increased and could be influenced by other factors such as immune activation and erythropoiesis.
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PMID:Soluble CD23 and other receptors (CD4, CD8, CD25, CD71) in serum of patients with chronic lymphocytic leukemia. 825 2

The aetiology of GS remains obscure and a little is known about the immune competence of these patients. Interestingly, all children with OOGS were from low 'socio-economic status' and showed diminished delayed hypersensitivity reactions and reduced T cell counts (E-R) in our previous observation. We present herewith a preliminary data on evaluation of T cell sub-populations determined by monoclonal antibodies (CD3, CD4, CD8 and CD16 cells) in 10 patients with OOGS and AML prior to treatment. Quantitative immunoglobulin determinations of IgA, IgM, IgG were also made. The percentage of Pan T (CD3), CD4, CD8 cells were significantly lower than those in the controls (p < 0.01). The immunoglobulin levels were slightly elevated suggesting normal B cell functions. In conclusion, these preliminary findings suggest that cellular immune deficiency may be an underlying cause.
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PMID:T-lymphocyte sub-populations in orbito-ocular granulocytic sarcoma (OOGS) and acute myelocytic leukemia (AML): a preliminary study. 826 55

Transplantation of bone marrow autografts activated by culture in interleukin-2 (IL-2) followed by administration of IL-2 represents a novel approach in an attempt to combine ex vivo purging and post-transplant in vivo immunotherapy, and initial clinical results have suggested its feasibility. To further characterize the mechanism of the in vitro anti-leukemia effect, fresh bone marrow from normal donors and from patients with acute myelogenous leukemia (AML) in remission was cultured for 6 days in the absence or presence of IL-2 (1000 IU/ml). Proliferation of CD3, CD8, CD14, and CD56 cells was determined by direct immunofluorescence using flow cytometry. Predominantly T-lymphocytes (CD3+) and to a lesser extent CD56+ natural killer (NK) cells proliferate in 6-day marrow cultures in IL-2. Fresh bone marrow cells have no measurable NK activity when tested against K562 and Daudi target cell lines in a 4 h chromium-51 release assay, and it requires at least 6 days of culture in IL-2 to develop optimal cytotoxic activity. Cytokines released in the supernatants of these cultures were measured by immuno- and bioassays. Tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and IL-6 were found to be produced in significant amounts by marrow mononuclear cells during culture in IL-2. Even without IL-2 present, concentrations of these cytokines were increased in 6-day marrow cultures. In contrast, IL-3, IL-7, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) were below the level of detection of the immunoassay, a result that could be confirmed for GM-CSF and IL-3 by bioassay. The data suggest that culture of marrow from normal donors as well as from patients with AML obtained in remission can generate anti-leukemia effector mechanisms which are non-crossreactive with chemo- and radiotherapy and may contribute to effective ex vivo purging of residual leukemic cells. The transplantation of such IL-2 'primed' marrow may also contribute to an in vivo graft-versus-leukemia effect.
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PMID:Culture of normal and leukemic bone marrow in interleukin-2: analysis of cell activation, cell proliferation, and cytokine production. 837 89

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.
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PMID:In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity. 848 27


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