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)

The clinical status of a homogeneous cohort of long-term survivors of allogeneic marrow transplantation was assessed and residual leukaemia was studied by reverse transcription polymerase chain reaction for leukaemia specific BCR-ABL mRNA. The group comprised 34 consecutive patients with CML in chronic phase treated by chemoradiotherapy and transplantation of bone marrow from HLA-identical sibling donors between February 1981 and December 1983 in the joint Hammersmith-Northwick Park programme. The probability of survival at 10 years was 59 +/- 17%. Eighteen of the 19 surviving (95%) patients have Karnofsky scores of 90 or 100% indicative of a good performance status. One of the survivors had evidence of relapse 6.5 years after transplant but has since been restored to complete remission by treatment with interferon-alpha followed by donor leucocyte transfusions. Surprisingly, 2 of the 19 patients who have been in remission for over 10 years have molecular evidence of persisting leukaemic cells. Quantification by competitive PCR indicated that the malignant clone persisted at low levels. The data suggest that the majority of long-term survivors after BMT for CML are in good health and may be regarded as cured. Some long-term survivors, however, may still harbour residual leukaemic cells and continued monitoring for late relapse is warranted. Late relapse is amenable to further therapy with leukocyte transfusions from the original marrow donor.
 ...
PMID:Detection of residual leukaemia more than 10 years after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. 785 36

In the past two decades there have been a number of advances in the treatment of chronic myeloid leukemia (CML) in chronic phase. There has been very little progress in the management of advanced disease. Hydroxyurea and interferon-alpha have replaced busulfan as first-line therapy in chronic phase. Hydroxyurea provides excellent control of the disease for periods of months or years and has little toxicity. Interferon-alpha induces a reduction in the Philadelphia chromosome in a substantial minority of patients. Interferon-alpha may also prolong survival. Neither hydroxyurea nor interferon-alpha is able to cure the disease. Patients in chronic phase may be cured by allogeneic bone marrow transplantation (BMT). This procedure has a number of limitations, however, including limited availability, high cost, and substantial morbidity and mortality. Current challenges in BMT are to increase its applicability, to reduce graft-versus-host disease, and to augment graft-versus-leukemia effects. The role of autologous transplantation in CML remains speculative.
 ...
PMID:Approaches to the treatment of chronic myeloid leukemia. 791 35

Although the diagnosis of rare eosinophilic leukaemia is possible based on cytogenetic abnormalities, the chromosomal aberrations reported are diverse. We found a t(2;5) (p23;q35) translocation on bone marrow cells of a patient with chronic eosinophilia who suffered from multiple pustular folliculitis but lacked the clinical symptoms commonly observed in hypereosinophilic syndrome. No morphological abnormalities in an eosinophilic series were apparent and other haemopoietic cells were well preserved. A therapeutic trial with interferon-alpha failed after a 2-month period, and the patient is currently undergoing a combination therapy with interferon and intermittent administrations of hydroxyurea.
 ...
PMID:Eosinophilic leukaemia with a t(2;5) (p23;q35) translocation. 794 87

A novel expression vector for human cells, pIFP, which expresses a cloned gene under the control of the human interferon-alpha-encoding gene (IFN-alpha) promoter (pIFN) was constructed. As a model of glycoprotein production, a human erythropoietin-encoding cDNA (EPO) inserted downstream from pIFN in pIFP was introduced into human B-cell leukemia-derived BALL-1 cells, and EPO-producing cells were established. Upon stimulation with Sendai virus, the cells produced human EPO at high levels. The highest production level and the highest inducibility were 872 IU/ml and 67-fold, respectively. Simultaneously, the transformed cells also produced IFN-alpha and tumor necrosis factor-alpha (TNF-alpha), as the parental BALL-1 cells did. Comparing the amounts of the substances produced, activity of the exogenous pIFN introduced seemed much higher than that of the endogenous one. Further, the transformed cells could be obtained in a large quantity by being applied to the 'in vivo cell proliferation method (hamster method)'. Human EPO produced by the transformed cells had a molecular mass range of 35 to 42 kDa, similar to that of EPO produced by CHO cells. The processing of EPO seemed to occur properly. The combination of the human pIFN, BALL-1 cells and the hamster method provides us with a useful production system for bioactive glycoproteins of human origin.
 ...
PMID:A high-level and regulatable production system for recombinant glycoproteins using a human interferon-alpha promoter-based expression vector. 803 16

The production of interleukin-2 (IL-2) by phytohemaglutinin (PHA)-stimulated cells of human leukemia T cell line MOLT-16 can be significantly increased by interleukin-1 (IL-1) or interferon-alpha (IFN-alpha). The enhancing effect of IL-1 and IFN-alpha on IL-2 production was studied at the IL-2 mRNA level. We show that IL-1 enhances considerably and transiently, with the maximum level between 1 and 2 hr after stimulation, the expression of IL-2 mRNA in the PHA-stimulated cells. The level of IL-2 mRNA declined rapidly within 4 to 6 hr after stimulation in both PHA- and PHA plus IL-1-stimulated cell cultures. On the contrary, IFN-alpha does not elevate the level of IL-2 mRNA above the level in PHA-stimulated cultures, but maintains an enhanced level of IL-2 mRNA in the activated cells for more than 6 hr after stimulation. These observations correlate well with the kinetics of IL-2 protein production into the culture media. The results thus suggest that IL-1 and IFN-alpha may exert an enhancing effect on IL-2 production by distinct mechanisms. In addition, none of the five other lymphokines tested (i.e., IL-2, IL-3, IL-4, IL-5, and IL-6) had any significant effect on IL-2 mRNA expression in the activated MOLT-16 cells.
 ...
PMID:Interleukin-1 and interferon-alpha augment interleukin-2 (IL-2) production by distinct mechanisms at the IL-2 mRNA level. 806 32

A 57-year-old woman was admitted because of weakness, fatigue, abdominal discomfort, easy bruising and splenomegaly. A highly elevated leukocyte count with hairy-cell-like cells was found, the cells being positive for the monoclonal antibodies CD19, FMC7, CD11c and B-ly-7 and negative for CD24 and CD25. Blood and bone marrow were investigated not only in our own laboratory but also in several other laboratories resulting in a variety of possible diagnoses. Only after combining all data could a definitive diagnosis of variant hairy cell leukaemia be made. The patient was treated initially with a splenectomy and later on with interferon-alpha-2b, resulting in a steady decrease in the leukocyte count. After a follow-up of 2 years a nearly complete remission was obtained with a good quality of life. The differential diagnosis of this rare disorder is discussed with emphasis on the relative contribution of different diagnostic procedures.
 ...
PMID:A patient with a variant form of hairy cell leukaemia. 810 34

We have previously shown that interferon-alpha (IFN-alpha) augments interleukin-2 (IL-2) production in mitogen-activated but not unstimulated T cells (1). Here, we studied the effect of IFN-alpha on activation-driven cell death (apoptosis) using a human leukemia T cell line, MOLT-16, as a T cell activation model. IFN-alpha alone had no effect on either the IL-2 production or apoptosis of MOLT-16 cells, but significantly increased both the IL-2 production and apoptosis in the MOLT-16 cells after phytohemagglutinin (PHA) stimulation as determined by CTLL-2 assay and by flow cytometric analysis using propidium iodide (PI) staining. Since IL-2 has been shown to induce apoptosis in some systems, we next evaluated whether the apoptosis in MOLT-16 cells was due to endogenous IL-2 production upon PHA stimulation. However, the addition of exogenous IL-2 to unstimulated cultures of MOLT-16 did not induce DNA fragmentation, a characteristic feature of apoptosis, as determined by DNA electrophoresis and by flow cytometric analysis with PI-stained cells. Furthermore, anti-IL-2 antibody did not prevent PHA-induced DNA fragmentation in MOLT-16 cells. Thus, we conclude that both PHA-induced IL-2 production and apoptosis are outcomes of T cell activation and that IFN-alpha may exert immunoregulatory effects on T cell activation by augmenting both processes.
 ...
PMID:Natural human interferon-alpha augments apoptosis in activated T cell line. 818 Oct 67

Suppression of c-myc expression is observed during induced differentiation of several myeloid cell lines and it has been attributed to the cell growth arrest that accompanies terminal differentiation. To dissect the role of c-Myc in the proliferation-differentiation switch we have studied c-myc expression in K562 cells exposed to several chemical agents. This model system allowed us to discriminate between the growth arrest and differentiation phenomena as well as the induction of differentiation along two different lineages (erythroid and myelomonocytic). Our results showed that c-myc expression did not significantly decrease when growth inhibition is reversible, either by treatment with a differentiating agent such as hydroxyurea (which induced erythroid differentiation) or by a non-differentiating agent such as interferon-alpha. In contrast, c-myc expression decreased when cells underwent terminal differentiation, either along the myelomonocytic (by 12-O-tetradecanoylphorbol-13-acetate) or erythroid (by 1-beta-D-arabinofuranosylcytosine) lineages. These results indicated that c-myc down-regulation is not obligatory for growth arrest and non-terminal differentiation of human myeloid cells. In contrast, c-myc down-regulation occurred in terminal differentiation, but induction of myelomonocytic differentiation resulted in a greater loss of c-myc mRNA than induction of erythroid differentiation.
Leukemia 1993 Nov
PMID:Down-regulation of c-myc gene is not obligatory for growth inhibition and differentiation of human myeloid leukemia cells. 823 Dec 50

In 1983 was for the first time reported that natural interferon-alpha (IFN-alpha) has a cytoreductive effect when used for treatment of chronic myelogenic leukemia (CML). The following studies using natural as well as recombinant IFN-alpha preparations confirmed the high remission rates with this therapy (70% CR and more than 30% cytogenetic responses) in patients with CML. Flu-like symptoms are recorded in more than 90% of the patients in the initial therapy phase. IFN-alpha seems to have no activity in patients in accelerated phase or blast crisis. High doses of IFN, i.e. more than 4,000,000 per day, achieve high response rates. Responses correlate with risk factors. New possibilities for improvement of therapy results with IFN are the combinations of IFN with other therapy modalities or concepts such as chemotherapy and/or bone marrow transplantation.
 ...
PMID:[Interferon-alpha therapy in chronic myeloid leukemia]. 827 64

We demonstrated earlier that post-exposure prophylaxis with 3'-azido-3'-deoxythymidine (AZT, zidovudine) or with AZT + interferon-alpha (IFN-alpha) prevented viremia and disease in BALB/c mice inoculated with Rauscher murine leukemia virus (RLV). After the 20-day treatment course, most animals were resistant to rechallenge with live virus. Adoptive transfer of T cells from such resistant but not from normal mice into naive recipients provided full protection against virus challenge. From these experiments, we concluded that post-exposure chemoprophylaxis restricted virus replication and allowed the animals to form protective, long-lasting cellular immune responses. Here, the role for cellular immunity during antiviral chemoprophylaxis was tested by comparing treatment success in normal BALB/c mice and in their nude, athymic counterparts. Both were inoculated with equal doses of RLV (10(4) plaque-forming units, pfu). Single-agent AZT or combination therapy with AZT + IFN-alpha, started before or after RLV inoculation, prevented viremia in all normal but not in most nude mice. A significant number of nude mice were completely protected by chemoprevention only when given a 10 times lower virus dose. When normal mice were injected with a 10 times higher virus dose (10(5) pfu), complete protection by chemoprevention was lost. These results demonstrate that the success of chemoprevention depends critically on the virus inoculum. The differential success of chemoprevention in normal and T-cell-deficient mice implies that effective cellular immunity plays an important role in protecting virus-exposed animals against viremia and disease.
 ...
PMID:Chemoprevention of retroviral infection: success is determined by virus inoculum strength and cellular immunity. 828 40


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