Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances of cytogenetics in human hematological malignancies and solid tumors were reviewed. In leukemia and lymphoma, many non-random chromosome aberrations have been found in the last decade. Further specific chromosome aberrations, which existed usually in less than five percent of acute leukemia cases, were recently found, including t (1 ; 3) in MDS or AML M4, +der (1) t (1 ; 7) in MDS, t (1 ; 11) in AML M4 or M5 and +4 in AML M2 or M4. Recurrent chromosome deletions of 17p-, 9q- and 2p- were also found as secondary aberrations in association with tumor development. Accumulation of the data from variant translocation for the 9 ; 22, 8 ; 21 and 15 ; 17 gave us important informations of critical sites of the chromosome in leukemia development. A new trial for the simultaneous analysis of morphology, immunologic phenotype and karyotype on the same metaphase clearly demonstrated stem cell origin of leukemia in some cases, specializing the affected cell lineage. Progress in non-radioactive in situ hybridization techniques now allows approaches to the recognition of particular chromosome abnormality in metaphase and also in interphase cell by means of specific repetitive probes for each chromosome. Though a hypothesis that fragile sites may act as factors predisposing to chromosomal rearrangements have attracted attention in past few years, recent results appear to be conflicting without any direct proof. Cytogenetic studies in solid tumor have been remarkably progressed with advances of methodology. Recurrent chromosome aberrations in solid tumor were found, such as t (X ; 18) in synovial sarcoma, t (12 ; 16) in liposarcoma, and i (12p) in seminoma. Studies on the correlation between specific chromosome changes and histologic subtypes resulted in an useful orientation to the diagnosis and the therapy. Advance in cytogenetics may serve as new concepts for patho-physiology of malignant tumors and contribute to further understandings of molecular genetics in human solid tumors.
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PMID:[Cancer and chromosomes]. 268 17

The various etiologies of spontaneous hemarthrosis in adolescents and adults are reviewed: they include systemic diseases and local or regional disorders of the bones or joints. Among systemic diseases, the two main causes are coagulation disorders and hemoglobinopathies. Coagulation disorders may be either acquired (leukemia, thrombopenia, and hypoprothrombinemia induced by anticoagulant drugs with hemarthrosis being one of the major complications) or inherited (hemophilia which is not considered here, von Willebrand disease, and congenital thrombopathies). Hemoglobinopathies, particularly sickle-cell disease, are responsible for hemarthrosis in a few patients. Among local or regional disorders of the bones or joints, tumors such as hemangioma or synovial sarcoma are uncommon causes. Hemarthrosis is the main feature of pigmented villonodular synovitis. Hemarthrosis may occur in degenerative and metabolic diseases: while it is extremely rare in arthritis, it is frequently encountered in articular chondrocalcinosis which is the first diagnosis to consider when hemarthrosis occurs in an elderly patient. The search for an etiology, which is often difficult, should include a review of prior illnesses, a study of coagulation, and local clinical, radiological and biological investigations, with a study of the synovial fluid; in some instances, arthroscopy, synovial biopsy and even surgical exploration are required. Management includes rest, analgesics, antiinflammatory drugs and, above all, arthrocentesis which is essential for the prevention of articular damage and functional sequellae. Specific therapy is dependent on the etiology. In recurrent hemarthrosis, isotopic synoviorthesis may ensure lasting resolution of the effusion.
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PMID:[Spontaneous hemarthrosis in adolescents and adults, excluding hemophilia]. 629 20

A 16-year-old boy was operated upon for synovial sarcoma of the right thigh and underwent chemotherapy consisted of adriamycin (320 mg), cisplatin (780 mg), etoposide (4,200 mg) and ifosfamide (30,000 mg). He developed secondary leukemia 18 months after the chemotherapy. Acute lymphoblastic leukemia (L3) was initially diagnosed because of poor staining of alpha-naphtyl butylate esterase and induction chemotherapy with the LVP regimen (L-asparaginase 5,000 U/m2 day 8-21, vincristine 1.5 mg/ m2 day 1, 6, 11, 16, 21, 26, prednisolone 40 mg/m2 day 1-28) was performed. After the therapy was initiated, the leukemia was finally diagnosed as acute momocytic leukemia (M5a) because of the following data; blasts were positive for CD33 and HLA-DR and negative for CD10, CD19 and CD20; serum lysozyme was 104.0 micrograms/ml; re-evaluation revealed that blasts were strongly positive for alpha naphtyl butyrate esterase in a small part of the slides; 95% of the bone marrow cells showed t (9; 11) chromosomal aberration; gene rearrangement was positive for MLL and negative for JH, JK and TCR C beta 1. Nevertheless, complete remission was obtained after 1 course of LVP therapy. He received bone marrow transplantation from an unrelated volunteer donor after 3 courses of consolidation therapy. He has remained in complete remission for 16 months.
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PMID:[Complete remission achieved by L-asparaginase, vincristine and prednisolone (LVP) therapy in secondary leukemia (M5a type) with an MLL gene rearrangement]. 905 68

We have examined the use of the LDH (lactate dehydrogenase) assay for chemosensitivity testing in established and primary cultures of sarcoma, leukaemia and ovarian cancer in parallel with the MTT assay. The method we describe is rapid, sensitive and ideal for 96-well plate assays using adherent or suspension cultures. Excellent agreement between the two methods was observed (r = 0.936) using a variety of antitumour agents, with some notable exceptions. In the Bax (human synovial sarcoma) cell line MTT colour production by control cells was very low, thus MTT-->formazan production could not be relied upon as a definitive end point equating with cell number. In contrast, colour production of control cells using the LDH assay was significantly greater and all cultures tested were suitable for titration of chemosensitivity. There was a discrepancy between IC50 values obtained either by cell counting or MTT in the HTB88 (human leiomyosarcoma) line treated with 5-FU (59.9 microM vs > 200 microM, respectively). However, cell counting agreed well with the LDH assay (IC50 47.3 microM). Whilst the MTT assay remains a reliable method for chemosensitivity testing, the LDH assay may prove more appropriate in certain experimental settings.
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PMID:Chemosensitivity testing of fresh and continuous tumor cell cultures using lactate dehydrogenase. 906 57

It is now well recognized that chromosomal translocation followed by overexpression of a chimeric gene product plays a critical role in tumorigenicity in various malignant tumors, especially those of leukemia, malignant lymphoma, and soft-tissue tumors. In these malignant tumors, specific chimeric gene products are directly related to tumorigenicity. Therefore, if chimeric gene products could be observed in situ, it would be advantageous not only for the correct diagnosis of each tumor but also to improve our understanding of the basis of tumorigenicity. Accordingly, it would seem that reverse transcriptase (RT) in situ polymerase chain reaction (PCR) is a powerful and useful approach for the study of chimeric gene products in situ. Here, we introduce the application of RT in situ PCR to detect a hybrid, SYT-SSX messenger RNA in synovial sarcoma. We expect that the principle of this protocol also may be applied to detect other chimeric gene products.
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PMID:Application of reverse transcription in situ PCR in cancer analysis. 1686 63

Expression of CD69 on neutrophils and generation of anti-CD69 autoantibodies in patients with rheumatoid arthritis (RA) have been reported. Thus natural ligands for CD69 not yet identified and/or the anti-CD69 autoantibodies possibly affect neutrophils by evoking CD69 signaling, which may further affect joint-composing cells in RA. However, the effect of the CD69 signaling in neutrophils remains largely unclear. To elucidate the issue, we tried to identify proteins affected by the crosslinking of CD69 on neutrophils using a proteomic approach. Specifically, CD69 on granulocyte-macrophage colony stimulating factor (GM-CSF)-activated neutrophils was crosslinked by anti-CD69 monoclonal antibodies, and then intracellular proteins were detected using 2-dimensional electrophoresis and further identified by mass spectrometry and subsequent protein database searching. As a result, we successfully identified multiple proteins that increased their production by the CD69 signaling. Among the proteins, we focused on one of the up-regulated proteins, S100A9 calcium binding protein (S100A9), and investigated proteome changes brought by a recombinant S100A9 in a human synovial sarcoma cell line (SW982), a human chondrosarcoma cell line (OUMS-27), and a human T leukemia cell line (Jurkat). This revealed that the recombinant S100A9 altered proteomes of SW982 and OUMS-27, and to a lesser extent, that of the Jurkat cells. Further, S100A9 induced IL-1beta production from neutrophils and the SW982 cells. These data suggest that unidentified natural ligands for CD69 and/or the anti-CD69 autoantibodies possibly affect joint-composing cell types through the increased production of S100A9 in neutrophils, providing a new insight into functions of CD69 on neutrophils in RA.
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PMID:Crosslinking of the CD69 molecule enhances S100A9 production in activated neutrophils. 1723 3

We describe the emerging role of Synovial Sarcoma X breakpoint 2 Interacting Protein (SSX2IP) in cancer and its still largely unknown function in human cells. In rodents, SSX2IP has been shown to play a role in adherens junctions and cell adhesion, while in chickens SSX2IP was identified by virtue of its regulation by the light cycle and circadian rhythms. In humans, SSX2IP was identified through its interaction with the cancer-testis gene SSX2. However SSX2IP is expressed in a range of normal and fetal tissues unlike SSX2. SSX2IP containing constructs indicated that SSX2IP could be expressed in the nucleus and cytoplasm of transfected human cells, however, SSX2IP expression has been subsequently shown to peak on the surface of myeloid leukaemia cells during mitosis. Here we discuss the current knowledge of SSX2IP function in several species and the growing evidence that SSX2IP may be a suitable target for leukaemia immunotherapy.
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PMID:SSX2IP: an emerging role in cancer. 1790 21

SSX, a family of genes clustered on the X chromosome, has been identified as a cancer-testis antigen and also forms a part of the SYT-SSX fusion gene found in synovial sarcoma, implying that it has an important role in tumorigenesis. However, knowledge of the molecular regulation of SSX is still limited. In this study, we demonstrate that SSX or its SYT fusion protein is distributed as nuclear speckles, in which it is co-localized with B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1), which is a core factor of polycomb repressor complex 1. The C-terminal residues of SSX are indispensable for the nuclear speckle distribution, while the N-terminal domain is necessary for the recruitment of Bmi1, indicating that intact SSX must be needed for interaction with Bmi1 both spatially and functionally. In addition, the N-terminus of SSX also proved to contain an intrinsic nucleolar localization signal, which mediates the nucleolar translocation of SSX in particular kinds of cell stress such as the oxidation of hydrogen peroxide or heat shock. This stress-induced translocation is reversible and accompanied by HSP 70 or p14ARF traffic, suggesting that SSX is a stress response gene. It is of note that nucleolar translocation of SSX can result in disassociation of SSX from Bmi1, with consequent down-regulation of Bmi1 activity. These novel findings regarding distinct domains of SSX and its interaction with Bmi1 may shed light on the mechanism by which synovial sarcoma develops and on the up-regulation of SSX in cancer cells.
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PMID:Subnuclear distribution of SSX regulates its function. 2368 68

The SWI/SNF multisubunit complex modulates chromatin structure through the activity of two mutually exclusive catalytic subunits, SMARCA2 and SMARCA4, which both contain a bromodomain and an ATPase domain. Using RNAi, cancer-specific vulnerabilities have been identified in SWI/SNF-mutant tumors, including SMARCA4-deficient lung cancer; however, the contribution of conserved, druggable protein domains to this anticancer phenotype is unknown. Here, we functionally deconstruct the SMARCA2/4 paralog dependence of cancer cells using bioinformatics, genetic, and pharmacologic tools. We evaluate a selective SMARCA2/4 bromodomain inhibitor (PFI-3) and characterize its activity in chromatin-binding and cell-functional assays focusing on cells with altered SWI/SNF complex (e.g., lung, synovial sarcoma, leukemia, and rhabdoid tumors). We demonstrate that PFI-3 is a potent, cell-permeable probe capable of displacing ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin, yet contrary to target knockdown, the inhibitor fails to display an antiproliferative phenotype. Mechanistically, the lack of pharmacologic efficacy is reconciled by the failure of bromodomain inhibition to displace endogenous, full-length SMARCA2 from chromatin as determined by in situ cell extraction, chromatin immunoprecipitation, and target gene expression studies. Furthermore, using inducible RNAi and cDNA complementation (bromodomain- and ATPase-dead constructs), we unequivocally identify the ATPase domain, and not the bromodomain of SMARCA2, as the relevant therapeutic target with the catalytic activity suppressing defined transcriptional programs. Taken together, our complementary genetic and pharmacologic studies exemplify a general strategy for multidomain protein drug-target validation and in case of SMARCA2/4 highlight the potential for drugging the more challenging helicase/ATPase domain to deliver on the promise of synthetic-lethality therapy.
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PMID:The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies. 2613 43

Identification of fusion genes in cancer is essential for pathological diagnosis and clinical therapy. Although methods for detection of fusion genes, such as fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (PCR), have been developed in last two decades, these methods are not ideal for detection of these genetic alterations owing to their high cost and time-consuming procedures. In this study, we developed novel application for detection of gene translocations using loop-mediated isothermal amplification (LAMP). We verified the amplified DNA products of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK), synaptotagmin and synovial sarcoma, X breakpoint (SYT-SSX), and immunoglobulin heavy chain gene and B cell leukemia/lymphoma 2 (IgH/BCL2) by real-time PCR, agarose-gel electrophoresis, and the naked eye after the LAMP procedure. Fusion genes were detected in samples diluted 103 times within 60 min. Because of the advantages of rapid amplification, simple operation, and easy detection without requiring sophisticated equipment or technical skill, LAMP may have potential applications as an on-site analytical approach in hospitals for pathological diagnosis and decision making regarding appropriate therapeutic approachs.
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PMID:Novel Application of Loop-mediated Isothermal Amplification for Rapid Detection of Gene Translocation. 2934 80


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