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

We demonstrated previously that cellfree supernatant of the B151K12 T cell hybridoma (B151-CFS) contained T cell-replacing factor (here in after referred to as B151-TRF1) capable of inducing growth and differentiation of antigen-activated B cells into antigen-specific plaque-forming cells (PFC). In the present study, we have identified in B151-CFS another unique lymphokine activity (referred to as B151-TRF2), which induces polyclonal differentiation of unstimulated B cells into IgM-secreting cells without concomitant stimulation of antigen, mitogen, or anti-Ig antibody. The B151-TRF2 activity induced polyclonal IgM PFC responses via the action on surface Ig-positive small resting B cells from normal unprimed mice. This activation was effective across an H-2 barrier, and apparently independent of the presence of T cells and accessory cells. Interestingly, the B151-TRF2 activity notably stimulated B cells of neonatal and mutant DBA/2Ha mice, which are nonresponders to B151-TRF1, whereas it failed to activate the xid B cells from CBA/N mice. To substantiate that B151-TRF1 and B151-TRF2 activities are mediated by mutually distinguishable molecules, an absorption experiment of B151-CFS was performed by utilizing DBA/2Ha B cells which are lacking in B151-TRF1 receptor. It was found that DBA/2Ha B cells could absorb B151-TRF2 activity but not B151-TRF1 activity. In contrast, murine chronic B cell leukemia BCL1 cells, which were shown to differentiate into IgM-secreting cells by stimulation with B151-CFS, selectively removed B151-TRF1 activity but not B151-TRF2 activity. Furthermore, biochemical analysis revealed that the B151-TRF2 was a heat (56 degrees C for 30 min)-sensitive protein with an apparent m.w. of 30,000 by gel filtration, whereas B151-TRF1 was a heat-resistant glycoprotein with m.w. of 50,000. In addition, it was shown that prostaglandin E2 selectively inhibited B151-TRF2-mediated B cell responses. These results demonstrate clearly that B151-TRF1 and B151-TRF2 are distinct B cell differentiation factors involved in the different activation pathways of distinct B cell subpopulations. The immunologic implication of B151-TRF2 activity in B cell differentiation is discussed in comparison with other lymphokines so far reported to activate small resting B cells.
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PMID:Identification of two distinct factors, B151-TRF1 and B151-TRF2, inducing differentiation of activated B cells and small resting B cells into antibody-producing cells. 351 74

The frequency of involvement of the nervous system (NS) among 266 patients seen at the University College Hospital (UCH), Ibadan, with a diagnosis of malignant lymphoproliferative diseases (MLPD) was determined. Only one of these patients who had a solitary spinal-cord involvement by Hodgkin's disease (HD) was considered to have primary lymphoma of NS. In all other cases, NS was only secondarily involved by MLPD. This was most commonly observed in association with Burkitt's lymphoma and occurred in 49.3 and 67% of such patients who were previously untreated or previously treated, respectively. Nervous system (NS) involvement at presentation was much less commonly observed in non-Hodgkin's (NHL), HD and acute lymphoblastic leukaemia (ALL) at the rate of 6.7, 4.4 and 0% respectively of previously untreated patients. The NS was the site of relapse in 63.6, 43, 12.5 and 0% in BL, ALL, NHL and HD, respectively. Intra-cranial NS disease was identified as a poor prognostic feature as this was associated with a reduction of the probability of prolonged survival from 48% to less than 20% among patients with intra-cranial and/or extra-cranial disease in BL. Management of MLPD with high rate of NS involvement should include effective delivery of chemotherapy into CFS, both by direct injection intrathecally and through filtration across the blood-brain barrier following high-dose intravenous injection of agents like methotrexate or cytosine arabinoside.
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PMID:Management of malignant lymphoproliferative disorders of the nervous system. 609 82

Febrile episodes occurring in 29 elderly patients (mean age 75 years) with leukemia, from 1988 to 1993, were reviewed. A febrile episode was defined as a temperature of 38 degrees C or greater for at least 6 hours. The number of febrile episodes was 64. The average was 2.2 febrile episodes per patient. Seventy-two percent of febrile episodes occurred when the patients had neutropenia below 100/microliters, while 16% occurred with neutropenia of 101/microliters to 500/microliters. Causative microorganisms were identified in 48% of total febrile episodes. The most common infectious site was the urinary tract which accounted for 25% of total episodes. Pneumonia and septicemia accounted for 22% of total episodes, respectively. Gram-positive cocci were responsible for 66% of microbiologically documented febrile episodes, while 21% were caused by gram-negative bacilli. Gram-positive cocci, particularly staphylococcus aureus, coagulae-negative staphylococcus and enterococci increased compared with a decade ago in our department. Granulocyte colony-stimulating factor (G-CSF) was used 12 times for infection. No significant difference in fever amelioration was seen between G-CSF and non-G-CFS cases.
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PMID:[Infection in elderly leukemic patients]. 886 21

Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.
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PMID:The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome. 2051 89

In October 2009 a team of researchers from the Whittemore Peterson Institute, in association with the National Cancer Institute and the Cleveland Clinic in the USA, made a discovery that could potentially open the door to useful treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The researchers, led by Judy Mikovits, discovered a significant correlation between ME/CFS and an infectious retrovirus called xenotropic murine leukaemia virus-related virus (XMRV). XMRV is classified as a gammaretrovirus, belonging to the same broad family as HIV, but more closely related to a group of viruses that cause cancers such as leukaemia. XMRV is the first member of the gammaretrovirus genus of retroviruses to be found in humans; the research to fully understand the connection between ME/CFS and XMRV, as well as what it means to have the virus, is ongoing. The disastrous impact of AIDS on human health has significantly raised the profile of retroviruses as human pathogens, and XMRV has potentially serious health implications not only for patients, but also for those caring for people with ME/CFS.
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PMID:XMRV: does this virus hold the key to myalgic encephalomyelitis/CFS? 2064 85

The xenotropic murine leukemia virus (MLV)-related viruses (XMRV) have been reported in persons with prostate cancer, chronic fatigue syndrome, and less frequently in blood donors. Polytropic MLVs have also been described in persons with CFS and blood donors. However, many studies have failed to confirm these findings, raising the possibility of contamination as a source of the positive results. One PCR reagent, Platinum Taq polymerase (pol) has been reported to contain mouse DNA that produces false-positive MLV PCR results. We report here the finding of a large number of PCR reagents that have low levels of MLV sequences. We found that recombinant reverse-transcriptase (RT) enzymes from six companies derived from either MLV or avian myeloblastosis virus contained MLV pol DNA sequences but not gag or mouse DNA sequences. Sequence and phylogenetic analysis showed high relatedness to Moloney MLV, suggesting residual contamination with an RT-containing plasmid. In addition, we identified contamination with mouse DNA and a variety of MLV sequences in commercially available human DNAs from leukocytes, brain tissues, and cell lines. These results identify new sources of MLV contamination and highlight the importance of careful pre-screening of commercial specimens and diagnostic reagents to avoid false-positive MLV PCR results.
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PMID:Detection of murine leukemia virus or mouse DNA in commercial RT-PCR reagents and human DNAs. 2220 95

Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect "stealth" infection, or that XMRV/HMRV never reached humans, have to be considered.
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PMID:Phylogeny-directed search for murine leukemia virus-like retroviruses in vertebrate genomes and in patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome and prostate cancer. 2231

Gammaretroviruses related to murine leukemia virus (MLV) have variously been reported to be present or absent in blood from chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients and healthy controls. Using subjects from New York State, we have investigated by PCR methods whether MLV-related sequences can be identified in nucleic acids isolated from whole blood or from peripheral blood mononuclear cells (PBMCs) or following PBMC culture. We have also passaged the prostate cancer cell line LNCaP following incubation with plasma from patients and controls and assayed nucleic acids for viral sequences. We have used 15 sets of primers that can effectively amplify conserved regions of murine endogenous and exogenous retrovirus sequences. We demonstrate that our PCR assays for MLV-related gag sequences and for mouse DNA contamination are extremely sensitive. While we have identified MLV-like gag sequences following PCR on human DNA preparations, we are unable to conclude that these sequences originated in the blood samples.
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PMID:Sensitivity of PCR assays for murine gammaretroviruses and mouse contamination in human blood samples. 2262 4

The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.
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PMID:A multicenter blinded analysis indicates no association between chronic fatigue syndrome/myalgic encephalomyelitis and either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus. 2299 30

We aimed at assessing the clinical significance of the levels of acute lymphoblastic leukemia (ALL) cells in samples of cerebrospinal fluid (CSF) during therapy. We studied 990 CSF samples from 108 patients, at the time of diagnosis (108) and at each time of intrathecal therapy (882). The proportions of leukemic cells in CSF samples were assessed by flow cytometry (FCM). Patients with central nervous system (CNS) involvement at diagnosis (FCM+) showed predominantly a T-ALL, and higher percentages of known negative prognostic factors: high risk group, higher white blood cell counts, normal karyotype, and the BCR-ABL fusion gene. No differences in relapse free survival (RFS) and overall survival (OS) were observed between FCM+ versus FCM- at diagnosis. Patients with CNS involvement during therapy showed significantly older age, and higher frequencies of T-cell leukemia. We found a significantly higher RFS in patients with FCM+ during therapy. The detection of subclinical CNS disease by FCM during maintenance was associated with significantly lower 3-years RFS and 3-years OS. A sensitive methodology like FCM can be applied for a close follow-up of the levels of ALL in CFS samples, and may identify a group of patients at high risk for relapse.
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PMID:Detection of occult cerebrospinal fluid involvement during maintenance therapy identifies a group of children with acute lymphoblastic leukemia at high risk for relapse. 2346 76


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