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)

Here we report a case with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. A 7-month-old Japanese boy was diagnosed to have NK cell leukemia based on the existence of abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-) /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The leukemic cells showed few azurophilic granules in the cytoplasm and weak cytotoxic activity. Although he presented with a huge mass occupying the bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete remission by the conventional chemotherapeutic regimen for acute myelogenous leukemia, followed by an unrelated cord blood transplantation. He has remained in complete remission for 14 months posttransplant. To our knowledge, this is the youngest reported case with precursor NK cell leukemia; cord blood transplantation may thus be the treatment of choice for this disease.
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PMID:An infant with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. 1134 48

We generated a monoclonal antibody (mAb) 6G7, which recognizes a 220-kD antigen on selected subpopulations of normal myeloid and lymphoid cells and their malignant counterparts. 6G7 reacts with 90-95% of peripheral blood B cells, 70-80% of CD8(+) cells, 30-35% of CD4(+) cells, 20-40% of monocytes, and 20-40% of CD34(+) cells from bone marrow. 6G7 reacts with leukemic blasts in acute myeloid leukemia (14/16), adult acute lymphoblastic leukemia (ALL) (5/5), pediatric ALL (5/9), chronic lymphocytic leukemia (8/8), follicular lymphoma (7/7), and Burkitt's lymphoma (1/1). Long-term bone marrow culture of 6G7(+/-) cells showed the majority of clonogenic hematopoietic cells were in mAb 6G7 subpopulation. An immunotoxin of 6G7 and ricin A chain was cytotoxic to 6G7(+) leukemia cell lines. mAb 6G7 has potential clinical applications for targeted immunotherapy of both leukemia and lymphoma.
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PMID:Characterization of a new monoclonal antibody 6G7 that recognizes a unique antigen on myeloid and lymphoid cells. 1135 71

The levels of hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders were investigated using a variety of approaches. Firstly, serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF and Flt3-ligand (Flt3L) were examined in acute leukemia patients with treatment-induced cytopenia and complicating bacterial infections. Increased serum levels of both G-CSF and Flt3-ligand (Flt3L) were detected when these patients developed therapy-induced leukopenia, whereas GM-CSF levels were low or undetectable. Development of complicating bacterial infections then increased the serum levels of both G- and GM-CSF, and the Flt3L levels remained high during the infections. Secondly, release of growth factors was characterized for clonogenic T cells that remained in the circulation of acute leukemia patients with chemotherapy-induced cytopenia. CD4(+) and CD8(+) T cells from these patients released high levels of GM-CSF, relatively low levels of IL-3 secretion having been detected, and only a minority of the clones released detectable amounts of Flt3L. Thus, circulating T cells may contribute to the high systemic growth factor levels in cytopenic patients. Thirdly, plasma levels of GM-CSF and interleukin-3 (IL-3) were examined in patients with malignant disorders who received chemotherapy plus G-CSF for stem cell mobilization. Increased levels of GM-CSF and Flt3L were detected both in the patients' plasma and in the stem cell grafts. Despite the increased growth factor levels in neutropenic patients with complicating infections, the occurrence of febrile neutropenia did not have a major impact on normal hematopoietic reconstitution (i.e. duration of treatment-induced neutropenia) after intensive chemotherapy for acute myelogenous leukemia.
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PMID:Hematopoietic growth factors in patients receiving intensive chemotherapy for malignant disorders: studies of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and Flt-3 ligand (Flt3L). 1139 10

Adoptive cellular immunotherapy has proven to be a successful approach in preventing and curing cytomegalovirus infection and Epstein-Barr virus-associated lymphomas after bone marrow transplantation. Translation of this approach for preventing leukemia relapse after bone marrow transplantation might require ex vivo priming and long-term maintenance of leukemia blast-specific T cells. To accomplish this goal, procedures were optimized for the in vitro priming of naive CD8 using dendritic cells activated by CD40 ligation, interleukin-12 (IL-12), and IL-7. Using T lymphocytes and dendritic cells obtained from HLA-matched allogeneic bone marrow transplantation donors and leukemia blasts as a source of tumor antigens, anti-acute myeloid leukemia cytotoxic T lymphocytes (CTLs) were induced. In these experiments, it was found that though it is possible to induce CTLs using immature dendritic cells, IL-12, and IL-7, obtaining long-term CTLs requires the presence of CD4 T cells in the priming phase. Using this approach, long-term antileukemia CTL lines could be generated from 4 of 4 bone marrow donors. Because this procedure does not require definition of the target antigen and because it selects responding cells from a virgin T-cell repertoire, its general application is suggested in adoptive immunotherapy and in the definition of tumor rejection antigens.
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PMID:Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy. 1171 75

Using red cell phenotyping (RCP) and/or cytogenetics (CYT) we identified 19 patients with persisting mixed chimerism (MC) among 231 patients transplanted with partially T cell-depleted stem cell grafts from HLA-identical siblings. Persisting MC is defined as MC for more than 2 years in patients without any evidence of relapse. Median leukemia-free survival in these patients was 150 (range, 50-218) months. Diagnoses were ALL (n= 10); AML (n = 2); CML (n = 2); NHL (n = 2); MDS (n= 1); MM (n = 1) and SAA (n = 1). Purpose of this study was the long-term follow-up of MC and definition of patterns of chimerism in the various subsets of PBMCs and granulocytes. Using a PCR-STR technique CD3(+)/CD4(+) (T4 lymphocytes), CD3(+)/CD8(+) (T8 lymphocytes), CD45(+)/CD19(+) (B lymphocytes), CD45(+)/CD14(+) (monocytes), CD45(+)/CD15(+) (granulocytes) and CD3(-)/CD56(+) (NK-cells) were analyzed. The majority of patients with persisting MC were conditioned with a less intensive conditioning regimen and had little GVHD. Sequential monitoring of the chimerism resulted in a group of patients (n = 7) with very slow transient mixed chimerism that resulted in complete DC after median 7 years. Another nine patients had a relatively high percentage of persisting autologous cells for a median of 12 years and in three patients we observed a stable low percentage of autologous cells. Only two out of 19 patients (AML-CR1, CML-CP1) relapsed during follow-up. Both patients had a relatively high percentage of autologous cells. Chimerism in granulocytes and PBMC subsets was analyzed at a median of 8 years after SCT in nine patients. In five patients mixed chimerism simultaneously detected by RCP and CYT was associated with MC in all subsets. Within each individual patient the percentages of donor and recipient cells were very different between the different subsets. Two CML-CP1 patients were mixed chimera in only two subsets and in one patient these subsets represented pending relapse. In another two patients mixed chimerism with a very low number of autologous red cells was not found in the PBMCs because of the different sensitivity level of the RCP and the PCR-STR technique. We conclude that in patients with persisting mixed chimerism after partially T cell-depleted SCT a remarkable number of patients had lymphoid malignancies, the majority of the patients were conditioned with less intensive conditioning regimens and the mixed chimerism was not correlated with relapse. Chimerism in granulocytes and PBMC subsets did show great intra-individual differences in the subsets and these data correlated well with RCP and CYT data with the exception of the NK cells.
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PMID:Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation. 1184 Feb 58

Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models. We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients. T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only. T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells. In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+). These results provide for the first time evidence for spontaneous T-cell reactivity against defined antigens in AML patients. These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
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PMID:CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. 1220 Mar 77

Early immune reconstitution after intensive chemotherapy for acute myelogenous leukemia (AML) occurs after 2-4 weeks of cytopenia, but T cell reconstitute is usually completed after several months. Interleukin-7 (IL-7) is a T cell growth factor involved in the late immune reconstitution, but its function during the early period of cytopenia has not been investigated. In the present study, we found that patients with untreated AML had decreased IL-7 serum levels, and induction chemotherapy had divergent effects on these levels. In contrast, patients in complete remission (CR) had intermediate levels immediately before consolidation therapy, and these levels decreased significantly when the patients developed therapy-induced cytopenia. Systemic IL-7 levels showed only minor increases during febrile neutropenia. Furthermore, IL-7 enhanced in vitro proliferative responses of polyclonal T cells derived from cytopenic patients, and the majority of circulating clonogenic CD4(+) and CD8(+) T cells from cytopenic patients could respond to both IL-2 and IL-7. To conclude, patients with untreated AML and severe chemotherapy-induced leukopenia (1) differ from other patients with CD4(+) T lymphopenia in that they show decreased IL-7 serum levels, and (2) the detection of circulating IL7-responsive T cells indicates that variations in systemic IL-7 levels are functionally important and contribute to an additional qualitative T cell defect in these severely T lymphopenic patients.
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PMID:Interleukin-7 (IL-7) in patients receiving intensive chemotherapy for acute myelogenous leukemia: studies of systemic IL-7 Levels and IL-7 responsiveness of circulating T lymphocytes. 1243 86

We have previously demonstrated a favorable effect of high-dose steroid in the treatment of children with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). This study was performed to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on the peripheral blood (PB) T lymphocyte subsets, and blast cells, during remission induction treatment in 23 children with newly diagnosed acute leukemia (16 with ALL, seven with AML). All patients were administered HDMP as a single daily oral dose of 30mg/kg for the first 4 days of induction therapy. The number of PB lymphocyte subsets (CD3, CD4, CD8, CD16+56, CD45RA, and CD45RO) were determined by flow cytometry before and after 4 days of HDMP treatment. While the number of PB blast cells significantly decreased, the absolute number of T lymphocytes expressing CD3, CD4, CD8, CD45RA and the absolute number of CD16+56 (natural killer) cells increased in all patients. We suggest that the beneficial effects of HDMP in the induction treatment of acute leukemia may occur partly due to an increase in the number of PB T lymphocyte subsets. A study randomly assigning patients to treatment with either conventional therapy or HDMP may provide further information.
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PMID:The effect of short-course high-dose methylprednisolone on peripheral blood lymphocyte subsets in children with acute leukemia during remission induction treatment. 1247 48

We have recently reported in an experimental model, that treatments based on the injections of dendritic cells which had phagocytosed apoptotic bodies derived from tumour cells were particularly effective in the cure of tumour-bearing animals. We proposed that systems using processing and presentation of antigenic molecules from antigen-presenting cells primed with apoptotic bodies can offer new opportunities in anti-cancer treatment. We first established the technical conditions for purification, characterisation and production of tumour cells isolated from fresh pleural liquid or blood. Then we compared efficacy of different apoptotic inducers agents on the cancer cells in culture. The apoptotic tumour cells were purified, characterised and maintained in coculture with monocytes-derived immature dendritic cells. We subsequently investigated the effect of the maturation process on phagocytosis of apoptotic bodies. We have shown that whatever the nature of the apoptotic cells they are phagocytosed by the dendritic cells which were efficiently matured using the combination of TNFalpha+Poly I:C. Furthermore, we demonstrated that the generation of the mature dendritic cells pulsed with apoptotic tumour cells, successfully generated CD4(+) (Th1) and CD8(+) (CTL) cells. All the experimental procedures that we have used were developed with clinical use in mind, using Good Manufacturing Products. We are presently investigating the feasibility of such a "vaccine" for the treatment of asbestos mesothelioma or acute myeloid leukaemia.
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PMID:Anti-cancer therapy using dendritic cells and apoptotic tumour cells: pre-clinical data in human mesothelioma and acute myeloid leukaemia. 1253 61

The objective of this study is to investigate the effect of vaccination with dendritic cells pulsed with survivin antigen on activation of antileukemic T cells, and inhibiting proliferation of leukemic cells. The expression of survivin on acute leukemic cells were detected by cofocal microscopy and immunoprecipitation-Western blot. DCs collected from peripheral blood mononuclear cells were pulsed with survivin purified proteins. Stimulation index (SI) and antileukemia CTL induction were analyzed with (3)H-TdR incorporation and (51)Cr releasing assay, respectively. The phenotype of T cells and DCs were identified by flow cytometry. By immunofluorescence of bone marrow and peripheral blood mononuclear cells, survivin expression was detected in 16 out of 19 AML cases (84.2%). The results showed that survivin fluorescence distribution was in cytoplasm. DCs from peripheral blood mononuclear cells were successfully induced, with typical DC morphologic characteristic. The vaccination with dendritic cells pulsed with survivin antigen dramatically stimulated the proliferation of T cells. The DCs loading survivin activated T cells with higher CD4(+) T(H) ratio as compared with DCs group, T cells activated with DCs expressed CD8 and CD56. Survivin DCs significantly inhibited the growth of leukemic cells in vitro. In conclusion, survivin antigen expressed in the cytoplasm of leukemic cells, leukemic vaccination with DCs pulsed with survivin antigen in vitro inhibited the proliferation of leukemic cells, that may be a pathway for therapy of leukemia.
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PMID:[Experimental study on activating antileukemic T cells by vaccination with dendritic cells pulsed with survivin]. 1266 93


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