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)

Human leukocyte antigen (HLA) class I expression at the allelic level was analyzed in 397 acute myeloid leukemia (AML) and 186 acute lymphoid leukemia (ALL) using a complement-dependent cytotoxicity assay. Impaired recognition possibly due to HLA downregulation was observed in 2% of the patients with AML and ALL in complete remission, and in 8%-15% in the groups with blasts. In 15 instances of diminished cytotoxicity, leukemic cells and control PHA blasts from the same patients were further analyzed using flow cytometry. In 4/6 ALL and 4/9 AML patients HLA downregulation or complete loss (2 patients) of cell surface expression could be confirmed. No genomic abnormalities were observed. In addition, 12 AML and 13 ALL patients were tested during relapse using flow cytometry. In 1/12 AML patients and 1/13 ALL patients allelic downregulation of cell surface expression was found. In two patients tested, downregulation or loss of cell surface expression of HLA class I antigens corresponded with impaired T cell mediated lysis by HLA restricted cytotoxic T lymphocyte.Treatment of the cells with alpha- or gamma-interferon could restore HLA class I expression and T-cell recognition. In conclusion, downregulation of cell surface expression of HLA class I expression at the allelic level in AML and ALL is infrequent but functionally relevant. HLA downregulation was reversible and T-cell recognition could be restored by alpha- or gamma-interferon.
 ...
PMID:Loss or downregulation of HLA class I expression at the allelic level in acute leukemia is infrequent but functionally relevant, and can be restored by interferon. 1187 38

There is currently no standard treatment for the blastic phase of chronic myeloid leukemia (CML-BC), which is a chemoresistant form of acute leukemia. Current approaches include using standard acute myeloid leukemia (AML) regimens in an effort to induce remission, variations of these approaches with drugs that seem more active in this specific leukemia, and the direct entry of patients into studies of investigational agents. Although the likelihood of achieving remission is small, immediate bone marrow transplantation in remission should be considered because it provides the only opportunity for long-term survival at this time. Allogeneic transplantation is preferred, but autologous transplantation of an early chronic phase marrow may provide benefit. Often, however, the duration of chemotherapy-induced remission of blast crisis is very short and may preclude entry into a transplant program. In addition, the patient may not be a candidate due to donor issues, age, or medical problems. If transplant is not an option, maintenance interferon is often used, although its benefit is uncertain. For patients in the accelerated phase of the disease, which is characterized by a variety of clinical presentations and cytogenetic abnormalities, the possibility of favorably manipulating the disease is greater. Again, there is no standard treatment, and clinical trials are recommended as first-line therapy. Treatment in the accelerated phase includes standard AML chemotherapy regimens, combinations of new agents, and the combination of cytostatic agents with interferon. Patients whose accelerated phase reverts to chronic phase after treatment may become candidates for bone marrow transplantation. However, current new approaches to the chronic phase applied in accelerated phase as well as new approaches directed specifically toward accelerated phase may lead to prolonged stabilization without bone marrow transplantation. In view of a median age of 55 at diagnosis of chronic phase, nontransplant regimens for accelerated phase that produce long-term benefit are urgently needed.
 ...
PMID:Accelerated and blastic phase of chronic myeloid leukemia. 1205 61

Rhabdomyolysis is an unusual complication of chemotherapy that can lead to substantial morbidity through such complications as renal failure, infections, and disseminated intravascular coagulation. The syndrome has been described after treatment with cyclophosphamide, 5-azacytidine, interleukin-2, and interferon and after bone marrow transplantation. We report a patient with acute myeloid leukemia who developed fulminant rhabdomyolysis after treatment with a cytarabine-containing regimen. The syndrome was complicated by acute renal failure requiring hemodyalisis, respiratory insufficiency, and pancreatitis. We suggest that the muscle damage might be related to the known ability of cytarabine to trigger the release of cytochrome c from the mitochondria, which could lead to uncoupling of the oxidative phosphorylation with subsequent depletion of ATP reserves at the skeletal muscle and rhabdomyolysis.
 ...
PMID:Acute rhabdomyolysis as a complication of cytarabine chemotherapy for acute myeloid leukemia: case report and review of literature. 1221 Aug 15

The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice. In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo. To determine the significance of earlier findings that expression of the tumor suppressor ICSBP is often downregulated in AML myeloblasts, AML1-ETO was introduced into BM cells derived from mice lacking the interferon regulatory factor ICSBP. Our findings demonstrate that AML1-ETO synergizes with an ICSBP deficiency to induce myeloblastic transformation in the BM, reminiscent of AML.
 ...
PMID:AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency. 1241 32

Real-time PCR is a new fluorometric method for cycle-to-cycle quantification of PCR product growth rates. The real-time PCR method is fast and associated with a high reproducibility rate. It is used more often for monitoring MRD and chimerism in patients after allogeneic stem cell transplantation (SCT). There are real-time PCR methods for patients with CML, AML and ALL patients with inv(16), t(8;21), t(15;17); t(1;19) and other chromosomal aberrations. For patients with AML monitoring MRD is useful to identify patients who were at high risk for relapse after receiving chemotherapy. In patients with CML monitoring MRD might be helpful to assess success of after allogeneic SCT, or response to therapies with interferon alfa or STI 571. We found, that it is possible to estimate the relapse stage in CML after SCT by the amount of bcr-abl fusion transcript detected using a real-time PCR method. The median measured bcr-abl amount differ significantly (P<0.001) between the various stages, which has relevant clinical implications because it enables early therapeutic decisions in relapsing patients after transplant as e.g. the application of DLI to induce graft-versus-leukemia effects. Using real-time PCR it is possible to detect differences at alleles between recipient and donor at a single nucleotide basis (SNP) for chimerism analysis. The real-time PCR method enables to achieve a high a sensitivity of up to 1x10(-4), which is much more sensitive than all other chimerism methods including VNTR-PCR, STR-PCR. Furthermore, chimerism in male recipients with a female donor can be monitored also by detecting y-chromosome specific sequences by real-time PCR after transplant, which might be the most sensitive method to detect host type gene sequences. All in all, new real-time PCR methods offer a fast, reliable and very sensitive method to evaluate MRD and chimerism in patients after allogeneic SCT and therefore, to help to identify patients who are at high risk for leukemic relapse.
 ...
PMID:Real-time PCR for monitoring minimal residual disease and chimerism in patients after allogeneic transplantation. 1243 Sep 26

Monocytic adaptor (Mona, also called Gads) is a molecular adaptor implicated in T cell activation and macrophage differentiation. The objective of this study was to identify elements regulating specific expression of Mona/Gads in human T cell and myelomonocytic cell lines. We first confirmed that the -2000 to +150 genomic region relative to the Mona gene transcription start site is sufficient to direct specific reporter gene expression in T cell lines, Jurkat, and MOLT-4 and in the immature myeloid cell lines, KG1a and RC2A. Deletion analysis and electrophoresis mobility shift assay identified several cis regulatory elements: overlapping initiator sequences, one interferon response factor-2 (IRF-2)-binding site at position -154, one GC box recognized by Sp1 and Sp3 at position -52, and two acute myeloid leukemia (AML)-1 binding sites at positions -70 and -13. Site-directed mutagenesis experiments indicated a key role of AML-1 for driving Mona expression in T cells and myeloid cells, and involvement of Sp1/Sp3 and IRF-2 transcription factors to modulate Mona expression in a cell-specific manner.
 ...
PMID:Characterization of promoter elements directing Mona/Gads molecular adapter expression in T and myelomonocytic cells: involvement of the AML-1 transcription factor. 1255 3

In this case report, we present a pediatric case of lymphomatoid granulomatosis (LG) with onset just after the completion of chemotherapy for childhood acute myeloid leukemia (AML). After the completion of maintenance therapy, the patient was admitted to our clinic with a complaint of cough. Radiologic examinations revealed nodular lesions in lungs, liver, and kidney. His bone marrow was in remission. The histopathologic examination of the open lung biopsy was consistent with LG. He received only one cycle of cyclophosphamide and high-dose methyl prednisolone treatment and continued to receive interferon (IFN) alpha-2b therapy for 18 months. This treatment regimen resulted in an excellent response. In conclusion, LG may occur after the treatment of pediatric AML as a rare complication and IFN alpha-2b may be an effective treatment choice in these patients.
 ...
PMID:A pediatric case of lymphomatoid granulomatosis with onset after completion of chemotherapy for acute myeloid leukemia. 1257 71

Systemic mastocytosis is a rare and occasionally aggressive condition that raises major diagnostic challenges. We report a case in a 72-year-old patient in whom the diagnosis of malignant mastocytosis required two bone marrow smears and three bone marrow biopsies examined using specific staining techniques. Despite interferon therapy, a mast-cell sarcoma of the sternum developed 1 year after symptom onset, followed 1 year later by acute myeloblastic leukemia, which was rapidly fatal.
 ...
PMID:Aggressive systemic mastocytosis. 1263 21

In this study, we analyzed the influence of cell cycle status manipulations of leukemic cells on Fas-mediated apoptosis using the GM-CSF-dependent human myeloid leukemia cell line AML-193 as a model. GM-CSF and long-term treatment with interferon-gamma (IFN-gamma) or interferon-alpha (IFN-alpha) were used to manipulate the cell cycle status. Control cells were GM-CSF deprived, nonproliferating cells. IFN-gamma or IFN-alpha treatment did not induce proliferation in control cells, but resulted in recruitment of cells from resting G(0) phase into activated G(1) phase. Using agonistic anti-Fas antibodies (FAS18), we demonstrated that this shift from G(0) to G(1) was accompanied by a 2.5-fold increase in Fas sensitivity. A similar increase in sensitivity to FAS18 could be obtained by induction of proliferation with GM-CSF. Quantitative FACS analysis of surviving cells after FAS18-induced apoptosis showed deletion of the G(1) compartment, but complete protection of resting G(0) cells. Cells in S or G(2)/M phase were relatively protected against Fas induction. In conclusion, sensitivity to Fas-mediated apoptosis was restricted to cells in G(1) phase of the cell cycle, and can be increased by treatment of cells with interferons. By this mechanism, interferon treatment may render leukemic cells more susceptible to lysis by T cells during immunotherapeutic interventions.
 ...
PMID:High susceptibility of human leukemic cells to Fas-induced apoptosis is restricted to G1 phase of the cell cycle and can be increased by interferon treatment. 1264 47

The existence of an immune based graft-versus-leukaemia (GvL) effect highlighted the prospect of managing relapsed leukaemias with T cell-based adoptive immunotherapy. Thus, various strategies have been explored for the in vitro expansion of acute myeloid leukaemia (AML)-specific T cells. In a popular approach, AML blasts have been genetically modified to express co-stimulatory molecules essential for effective T cell priming. One such tactic has been the modification of AML cells to express the B7/CD80 co-stimulatory molecule that binds to CD28 on T cells initiating events that culminate in enhanced cytokine production, proliferation and development of effector functions by T cells. The success of these strategies has been limited by difficulties in attaining sufficient transduction efficiencies and associated high levels of CD80 expression. We demonstrate that these problems can be circumvented by using anti-CD28 monoclonal antibody. Furthermore, we show that the synergistic relationship between CD80/CD28 pathway and interleukin 12 cytokine (IL-12), documented in the generation of cytotoxic T lymphocytes (CTL) for solid tumours, also applies to AML. CD28/IL-12 synergy facilitated the proliferation of allogeneic T cells in response to stimulation with primary AML blasts. The synergy also favoured generation of a Th1-type immune response, evidenced by gamma interferon (IFN-gamma) secretion and facilitated naive and memory T cell proliferation. Unlike some methods of in vitro T cell expansion, use of CD28/IL-12 synergy left T cells in the physiologically appropriate CD45RA-/CCR7- subsets known to be associated with immediate cytotoxic functions.
 ...
PMID:In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy. 1293 Mar 76


<< Previous 1 2 3 4 5 6 7 8 9 10