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)

This 2002 European Group for Blood and Marrow Transplantation (EBMT) activity survey concentrates on current status, increase and decrease in haematopoietic stem cell transplantation (HSCT) activity in Europe and investigates the association of transplant rates with team density. In 2002, there were 20 207 HSCT, 6915 allogeneic (34%), 13 292 autologous (66%) and 3947 additional re- or multiple transplants collected from 586 centres in 39 European countries. Main indications were leukaemias (6523 (32%; 76% allogeneic)); lymphomas (10 760 (53%; 92% autologous)); solid tumours (1913 (9%; 92% autologous)) and nonmalignant disorders (874 (4%; 92% allogeneic)). Compared to 2001, there were increases (>10%) for AML, ALL 1st CR, CML not 1st cP, MDS, SAA and CLL in allogeneic HSCT and for MDS, Ewing's sarcoma, soft-tissue sarcoma and ovarian cancer in autologous HSCT. Decreases (>10%) were observed in autologous HSCT for acute leukaemias beyond 1st CR, CML cP, glioma, breast cancer and lung cancer. Correlation of transplant rates (number of transplants per 10 million inhabitants) with team density (number of transplant teams per 10 million inhabitants) suggests different diffusion patterns for autologous compared to allogeneic HSCT. These data describe current practice for blood and marrow transplantation in Europe and give some hints about mechanisms involved in HSCT rates.
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PMID:Haematopoietic stem cell transplantation (HSCT) in Europe 2002. Changes in indication and impact of team density. A report of the EBMT activity survey. 1551 6

The usefulness of multiparameter flow cytometric (FC) analysis of cerebrospinal fluid (CSF) was evaluated in leukemia/lymphoma patients having central nervous system (CNS) involvement of the disease. In 12 specimens of 8 patients with different types of leukemia/lymphoma (one case of T-ALL, 3 cases of early B-cell ALL, one case of AML, and 3 proven or suspicious NHL cases) the presence of pathological clone in CSF has been confirmed or excluded. The phenotypic patterns of CSF cells were defined according to those of bone marrow (BM)/peripheral blood (PB) at diagnosis or during follow-up of the same patients. Furthermore, in one case of suspicious CNS infiltration of NHL, the pathological clone was characterized as a highly suspicious of solid tumor and was proved to be a lung cancer metastasis. The definition was made on the basis of CD45 (common leukocyte antigen) and other studied CD markers negativity. The exact comparison of immunophenotypic profiles of specimens from different sites (CSF, BM, PB) of the same patient has been performed and no phenotypic changes were found. In some CSF specimens, where no cells of suspicious pathological clone were detected, in 4-color analysis only normal lymphocyte population was found even in small cell samples (even if the cellularity was < than 0.3x10-6). In these populations the high values of T-cells (CD3+) predominated and the high prevalence of CD4+ over CD8+ cells, and an almost total lack of B-lymphocytes was found. Our results suggest that positive CSF immunology is a useful indicator of malignancy and reflects leptomeningeal involvement. Simultaneously we demonstrated that FC analysis of CSF in the aim to detect possible CSF seeding of leukemia/lymphoma is a reliable and quick technique.
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PMID:The value of multiparameter flow cytometry of cerebrospinal fluid involved by leukemia/lymphoma cells. 1564 Sep 38

There are few reports describing simultaneous occurrence of acute leukemia and lung cancer. We describe here an 83-year-old woman who simultaneously developed advanced adenocarcinoma of the lung and acute myeloid leukemia. She could not receive intensive chemotherapy due to poor performance status. This patient was treated with a combination of gefitinib, low-dose cytarabine and aclarubicin. This combination could be safely administered in the elderly patient with poor performance status and was effective for both lung cancer and acute myeloid leukemia.
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PMID:Successful treatment of a patient with synchronous advanced non-small cell lung cancer and acute myeloid leukemia by a combination of gefitinib, low-dose cytarabine and aclarubicin. 1608 Apr 96

The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.
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PMID:Investigation of the bovine leukemia virus proviral DNA in human leukemias and lung cancers in Korea. 1610 Apr 51

A nationwide survey of hematopoietic cell transplantation (HCT) was started in Japan in 1991, and the analyzed survey data have been presented as the annual report of the Japan Society for Hematopoietic Cell Transplantation. The 10-year overall survival (OS) rates after HCT for each disease are as follows: acute myelogenous leukemia, 44.2%; acute lymphocytic leukemia, 33.7%; adult T-cell leukemia, 24.6%; chronic myelogenous leukemia, 53.3%; myelodysplastic syndrome, 37.3%; non-Hodgkin's lymphoma, 41.5%; Hodgkin's lymphoma, 50.8%; aplastic anemia, 72.5%; breast cancer, 37.1%; germ cell tumor, 52.6%; and ovarian cancer, 44.2%. The 5-year OS rates for multiple myeloma and lung cancer were 40.6% and 23.6%, respectively. Except in cord blood transplantation, engraftment was accomplished in more than 90% of patients. The respective frequencies of acute graft-versus-host disease (GVHD) and chronic GVHD were 41.1% and 34.9% for related bone marrow transplantation (BMT), 66.8% and 34.5% for unrelated BMT, 52.9% and 36.0% for allogeneic peripheral blood stem cell transplantation, and 53.3% and 32.1% for allogeneic cord blood transplantation. OS for each disease was analyzed by patient age, stem cell source, donor type, disease status, and disease type. These data provide objective and valuable information for hematologists as well as for patients who need HCT.
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PMID:Current status of hematopoietic cell transplantation for adult patients with hematologic diseases and solid tumors in Japan. 1651 37

Sarcomatoid carcinoma of the lung (LSC) is a rare lung cancer characterized by an admixture of carcinoma and sarcoma components. Data concerning the genomic alterations of LSC are almost nonexistent. Here, we report on the first molecular cytogenetic characterization of a metastatic LSC. Cytogenetic and multicolor fluorescence in situ hybridization (M-FISH) analyses showed a near-triploid karyotype with numerous structural aberrations and four to six small supernumerary marker chromosomes containing chromosome 9 sequences. Comparative genomic hybridization on arrays (array CGH) detected an amplification of 9p23 approximately p24.3 and gains of 1q11 approximately q23.3, 3q26.2 approximately q29, and 17q23.2 approximately q24.1. The 9p amplification was also detected in the primary tumor and another metastasis of the same patient, indicating it was a significant element in the pathogenesis of this LSC case. Complementary FISH analysis showed that the small supernumerary chromosomes were isochromosomes for 9p23 approximately p24.3. These isochromosomes were lacking alpha-satellite sequences although they were still stable after 55 passages in culture. As demonstrated by immunostaining with anti-centromere antibodies, they contained a functional centromere. So-called analphoid "neocentromeres" are rare and have been mainly described in constitutional abnormal karyotypes. This case is the third description of the identification of neocentromeres in cancer, (i.e. well-differentiated liposarcoma and acute myeloid leukemia), and is the first one in a carcinoma. Our results suggest that the 9p23 neocentromere of this case of LSC might be similar to a 9p23 neocentromere previously identified in two constitutional cases. The frequency of neocentromere formation in solid tumors may indeed be underestimated and may have a significant implication in chromosomal instability in tumor cells.
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PMID:Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C. 1673 11

BCL-2 proteins are critical for cell survival and are overexpressed in many tumors. ABT-737 is a small-molecule BH3 mimetic that exhibits single-agent activity against lymphoma and small-cell lung cancer in preclinical studies. We here report that ABT-737 effectively kills acute myeloid leukemia blast, progenitor, and stem cells without affecting normal hematopoietic cells. ABT-737 induced the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. In cells with phosphorylated BCL-2 or increased MCL-1, ABT-737 was inactive. Inhibition of BCL-2 phosphorylation and reduction of MCL-1 expression restored sensitivity to ABT-737. These data suggest that ABT-737 could be a highly effective antileukemia agent when the mechanisms of resistance identified here are considered.
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PMID:Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. 1709 53

Sunitinib (SU011248) is an oral small molecular tyrosine kinase inhibitor that exhibits potent antiangiogenic and antitumor activity. Tyrosine kinase inhibitors such as SU6668 and SU5416 (semaxanib) demonstrated poor pharmacologic properties and limited efficacy; therefore, sunitinib was rationally designed and chosen for its high bioavailability and its nanomolar-range potency against the antiangiogenic receptor tyrosine kinases (RTKs)--vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). Sunitinib inhibits other tyrosine kinases including, KIT, FLT3, colony-stimulating factor 1 (CSF-1), and RET, which are involved in a number of malignancies including small-cell lung cancer, GI stromal tumors (GISTs), breast cancer, acute myelogenous leukemia, multiple endocrine neoplasia types 2A and 2B, and familial medullary thyroid carcinoma. Sunitinib demonstrated robust antitumor activity in preclinical studies resulting not only in tumor growth inhibition, but tumor regression in models of colon cancer, non-small-cell lung cancer, melanoma, renal carcinoma, and squamous cell carcinoma, which were associated with inhibition of VEGFR and PDGFR phosphorylation. Clinical activity was demonstrated in neuroendocrine, colon, and breast cancers in phase II studies, whereas definitive efficacy has been demonstrated in advanced renal cell carcinoma and in imatinib-refractory GISTs, leading to US Food and Drug Administration approval of sunitinib for treatment of these two diseases. Studies investigating sunitinib alone in various tumor types and in combination with chemotherapy are ongoing. The clinical benchmarking of this small-molecule inhibitor of members of the split-kinase domain family of RTKs will lead to additional insights regarding the biology, potential biomarkers, and clinical utility of agents that target multiple signaling pathways in tumor, stromal, and endothelial compartments.
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PMID:Sunitinib: from rational design to clinical efficacy. 1760 94

A low concentration of differentiation inducers greatly enhances the in vitro and in vivo antiproliferative effects of interferon (IFN)alpha in several human cancer cells. Among the differentiation inducers tested, the sensitivity of cancer cells to IFNalpha was most strongly affected by cotylenin A. Cotylenin A, which is a novel fusicoccane diterpene glycoside with a complex sugar moiety, affected the differentiation of leukemia cells that were freshly isolated from acute myelogenous leukemia patients in primary culture. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were early genes induced by the combination of cotylenin A and IFNalpha in carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFNalpha cooperatively induced apoptosis through the TRAIL signaling system. Combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells. In an analysis of various cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFNalpha in terms of the inhibition of cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to cisplatin, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from patients were also sensitive to the combined treatment in primary cultures. Combined treatment with cotylenin A and IFNalpha may have therapeutic value in treating human cancers including ovarian cancer.
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PMID:Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agents. 1764 78

To potentiate the response of acute myelogenous leukemia (AML) cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity, we have examined the efficacy of a combination with perifosine, a novel phosphatidylinositol-3-kinase (PI3K)/Akt signaling inhibitor. The rationale for using such a combination is that perifosine was recently described to increase TRAIL-R2 receptor expression and decrease the cellular FLICE-inhibitory protein (cFLIP) in human lung cancer cell lines. Perifosine and TRAIL both induced cell death by apoptosis in the THP-1 AML cell line, which is characterized by constitutive PI3K/Akt activation, but lacks functional p53. Perifosine, at concentrations below IC(50), dephosphorylated Akt and increased TRAIL-R2 levels, as shown by Western blot, reverse transcription-PCR, and flow cytometric analysis. Perifosine also decreased the long isoform of cFLIP (cFLIP-L) and the X-linked inhibitor of apoptosis protein (XIAP) expression. Perifosine and TRAIL synergized to activate caspase-8 and induce apoptosis, which was blocked by a caspase-8-selective inhibitor. Up-regulation of TRAIL-R2 expression was dependent on a protein kinase Calpha/c-Jun-NH(2)-kinase 2/c-Jun signaling pathway activated by perifosine through reactive oxygen species production. Perifosine also synergized with TRAIL in primary AML cells displaying constitutive activation of the Akt pathway by inducing apoptosis, Akt dephosphorylation, TRAIL-R2 up-regulation, cFLIP-L and XIAP down-regulation, and c-Jun phosphorylation. The combined treatment negatively affected the clonogenic activity of CD34(+) cells from patients with AML. In contrast, CD34(+) cells from healthy donors were resistant to perifosine and TRAIL treatment. Our findings suggest that the combination of perifosine and TRAIL might offer a novel therapeutic strategy for AML.
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PMID:Synergistic proapoptotic activity of recombinant TRAIL plus the Akt inhibitor Perifosine in acute myelogenous leukemia cells. 1901 Sep 14


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