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)

The polymerase chain reaction (PCR) has become a standard method for highly sensitive detection of the bcr/abl rearrangement in patients with chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). The exquisite sensitivity of the PCR facilitates the detection of residual leukemic cells after chemotherapy or after bone marrow transplantation. However, the detection of minimal residual disease does not yield any information on the malignant potential of the bcr/abl-rearranged cells. Qualitative PCR is therefore of limited prognostic value in the monitoring of residual leukemia. We have adapted the PCR for quantitative evaluation of cells carrying the bcr/abl rearrangement and by means of two exemplary cases of CML patients after bone marrow transplantation and under treatment with alpha-interferon, respectively, we show that this new technique is suitable for the long term follow-up of the activity of the residual bcr/abl rearranged clone. Longitudinal monitoring of residual disease by the technique presented provides a novel tool for detection of incipient relapse at a very early stage.
Leukemia 1992 Jun
PMID:Monitoring of residual disease in chronic myelogenous leukemia by quantitative polymerase chain reaction. 160 87

Fifteen chronic myelocytic leukemia patients in durable complete cytogenetic conversion (CCC) under interferon therapy, were monitored every three to six months by bone marrow (BM) karyotypes and/or reverse-transcription polymerase chain reaction (RT-PCR) on peripheral blood (PB) leukocytes (by a nested primer approach using two rounds of amplification, 30 cycles each). Special care was taken to minimize the risk of contamination. The median time of follow-up after first CCC was 12 months (range, 6-30). Thirty five BM karyotypes were performed. Only three patients demonstrated the transient reappearance of a few Philadelphia-positive metaphases, while other patients remained in CCC. Forty five PB samples were studied by RT-PCR. In two patients, no BCR/ABL transcript could be detected in three consecutive samples. In the 13 other cases, RT-PCR was intermittently negative, indicating a level of residual leukemic cells close to the threshold of sensitivity of the technique.
Leukemia 1992 Jun
PMID:Complete cytogenetic conversion in chronic myelocytic leukemia patients undergoing interferon alpha therapy: follow-up with reverse polymerase chain reaction. 160 97

The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyurea (HU) in conventional dosage. A clinical response was seen in seven patients treated with IFN-alpha 2b (4 CR and 2 PR), and in four patients treated with HU (3 CR and 1 PR). No significant side effects were observed. Our findings indicate that IFN-alpha 2b offers a non-leukaemogenic and very promising therapeutic alternative for E.T.
Leukemia 1992
PMID:Essential thrombocythemia--clinical features, therapy and follow-up of 12 cases. 160 10

Several laboratories have shown that AZT-resistant variants of HIV-1 can be isolated from patients who have received prolonged therapy with this drug. Our laboratory has now been able to generate HIV-1 variants resistant to both AZT and ddI, in tissue culture, by using step-wise increases in the concentrations of each of these compounds over a 10-week period. This work has been performed by culturing wild-type clinical strains of HIV-1 as well as the HIV-3b laboratory strain of this virus under such conditions. The ID50 values obtained for the resistant viruses thus generated vary between 50-100 times above those of the parental wild-type strains in each case. Furthermore, we have identified several new mutation sites in the HIV-1 pol gene that are responsible for the observed resistance to AZT and ddI. We have not succeeded, however, in generating drug-resistant strains of HIV-1, under conditions in which several compounds or anti-viral agents were simultaneously present during the in vitro selection process. Combinations of drugs which failed to yield drug-resistant variants included AZT plus ddI, AZT plus alpha-interferon, and ddI plus alpha-interferon. These findings indicate that HIV drug resistance is less likely to occur in tissue culture when combinations of drugs are used, and provide rationale for the development of combination clinical trials for treatment of HIV-associated disease.
Leukemia 1992
PMID:Generation of nucleoside-resistant variants of HIV-1 by in vitro selection in the presence of AZT or DDI but no by combinations. 160 23

Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated monocytes/macrophages, inhibits leukemic cell growth and may contribute to a graft-versus-leukemia effect after marrow transplantation. We examined the recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF), alone or in combination, for their ability to induce monocytes from normal donors and patients after marrow grafting to express TNF-alpha mRNA and secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by Percoll separation of E-rosette-negative cells, and cultured with cytokines under non-adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable in freshly isolated monocytes from normal donors. Only the combination of IFN-gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA transcript levels and protein secretion. Levels of TNF-alpha transcripts induced by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In contrast, greater than 80% of the total TNF-alpha bioactivity secreted by LPS-stimulated monocytes was secreted in the first 8 h. When monocytes were incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, both TNF-alpha mRNA expression and TNF-alpha protein production occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of tumor necrosis factor-alpha production and gene expression in monocytes. 161 21

Therapy with alpha-interferon (IFN alpha) can suppress the Ph1-positive hemopoiesis in a percentage of patients with chronic myelogenous leukemia (CML). We used IFN alpha to treat a 30-year-old CML patient, characterized by favourable prognostic signs (such as low leukocytosis, absence of splenomegaly and no increase in bone marrow blasts) at diagnosis, and obtained a complete remission, as evaluated by Southern blot and cytogenetic analysis, after one year of treatment. However, the polymerase chain reaction (PCR) revealed the persistence of a minimal residual disease. The IFN alpha therapy was stopped and the hematological status remained stable until eighteen months later, when a cytogenetic analysis revealed the appearance of a clone characterized by t(9;22) and trisomy 8, accounting for 30% of bone marrow metaphases. This cell population spontaneously regressed in the following months, before any cytotoxic treatment. However, as leukemic cells, detected by PCR, were still present, the patient received a high dose chemotherapy, which induced the complete eradication of the Ph1-positive clone, as demonstrated by the absence of bcr-abl transcript at the PCR reaction. Molecular and cytogenetic remission persist one year later, without any further therapy.
Leukemia 1992 Jul
PMID:Transient cytogenetic relapse in a Ph1-positive chronic myelogenous leukemia patient previously treated with alpha-interferon. 162 97

Early studies with the Gross passage A leukemia virus demonstrated that retroviral infection suppresses cellular and humoral immune responses. In extensive studies of the feline leukemia (FeLV) virus, which can induce profound immunodeficiency disease, are generative anemia and lymphoid, myeloid and erythroid neoplasia, the immunosuppressive effects of this retrovirus could be attributed to the actions of the retroviral envelope protein p15E. We found that a highly conserved, synthetic 17 amino acid peptide synthesized by Cianciolo and co-workers that is homologous to the hydrophilic portion of the otherwise hydrophobic transmembrane envelope protein can suppress polyclonal activation of B-cells, impair production of gamma- and alpha-interferon, inhibit production of interleukin-2, inhibit expression of IL-2 receptors, and suppress responses of cytotoxic lymphocytes. In analyses with inactivated preparations of the human immunodeficiency virus, with Pahwa et al. we demonstrated that purified non-infectious retrovirus and also retroviral proteins, in particular gp120, appeared to produce some of the immunosuppressive properties of HIV, particularly suppression of B-cell activation in response to known B-cell stimulants irrespective of T-cell influence, suppression of T-helper cell functions essential to B-lymphocyte responsiveness, and impaired function of immunoglobulin-secreting cells. Other investigators have also reported strong immunosuppressive or immunostimulatory influences for components of the HIV retrovirus and also gp120 through yet poorly elucidated but certainly complex actions on both T- and B-lymphocyte-mediated immune functions.
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PMID:In vitro immunomodulation and in vivo immunotherapy of retrovirus-induced immunosuppression. 166 53

Forty-seven patients with chromosome Philadelphia-positive (Ph1) chronic granulocytic leukaemia (CGL) in transformation underwent autologous transplantation of peripheral blood stem cells (ABSCT) collected at the original diagnosis before any treatment. They were treated with three consecutive strategies: single transplant (group I = 17 patients), double transplant (group II = 13 patients), double transplant followed by recombinant alpha interferon (group III = 17 patients). Forty-three patients were restored to a second chronic phase with a cytogenetic conversion (more than 10% Ph1-negative marrow metaphases) occurring in 14 of the 29 evaluable patients. Most patients had a recurrent transformation occurring 2-43 months after ABSCT and finally eight patients are still alive in second chronic phase 4-49 months after ABSCT (median = 24 months). The actuarial median duration of second chronic phase was 3 months, 10 months and 18 months for group I, group II and group III patients (P less than 0.0001). The encouraging results observed for group III patients prompt us to propose ABSCT for patients in chronic phase with initial prognostic factors, suggesting that recombinant alpha interferon will not be effective if administered as front-line therapy.
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PMID:Autologous blood stem cell transplantation for chronic granulocytic leukaemia in transformation: a report of 47 cases. 167 19

Recombinant interferon alpha enhanced the MHC class I antigen density on human leukaemia/lymphoma cell lines REH, U-937 and HL-60, as measured by immunocytofluorometry using specific monoclonal antibodies. A similar effect was induced (as demonstrated in REH cells), also by human leukocyte interferon-alpha. The latter, however, caused no major alterations in the expression of leukocyte common antigen (ICA; CD45) and transferrin receptor (CD71) in the cell lines examined. In REH cells, there was no interferon-induced alteration of CD10 antigen (CALLA), which in this cell line is markedly down-regulated by 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A decrease of CD4 antigen density on the cell membrane was induced by interferon-alpha in monoblastoid U-937 cells. No induction of MHC class I and II antigens by interferon-alpha was found in K-562 cell subline.
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PMID:Interferon alpha-induced modulation of leukocyte cell surface antigens: immunocytofluorometric study with human leukaemia/lymphoma cell lines. 168 18

One proposed therapeutic application of granulocyte colony-stimulating factor (G-CSF) is in differentiation induction therapy of myelodysplastic states (MDS) or acute myeloid leukemia (AML). G-CSF however has a substantial growth including effect which limits its potential as a differentiation inducing agent. We have therefore made a systematic search for agents which might restrain the proliferative effects of G-CSF whilst retaining the differentiation stimulus. Of all the agents we have tested on human bone marrow progenitor cells: (6-thioguanine, all-trans retinoic acid, vincristine, recombinant human alpha-2b and gamma-interferon) only the latter abolished the stimulation of cell growth and retained, or possibly increased, the differentiation effect of G-CSF. The antiproliferative drugs 6-thioguanine and vincristine both antagonized the neutrophil-granulocyte differentiation inducing action of G-CSF. Retinoic acid and alpha-2b interferon both had weak effects on proliferation and failed to enhance differentiation. These results suggest that it may be possible, by combining G-CSF with a suitable second agent, to utilize its substantial differentiation inducing effect without incurring the potentially hazardous effects of increased leukemic cell growth.
Leukemia 1990 Mar
PMID:Dissociation of the proliferation and differentiation stimuli of granulocyte colony-stimulating factor (G-CSF). 169 Mar 19


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