Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report aims to review briefly the current status of treatment of haematological malignancies with interferon-alpha (IFN-alpha). Overall hairy cell leukemia and chronic myelogenous leukemia appear to be most sensitive to IFN-alpha. We started to investigate, how interferon exerts its antileukemic activity and in which way interferon therapy can be optimized. Our preliminary results fail to support the view of interferon mediated enhancement of host responses. They rather indicate direct effects of IFN on leukemic cells in vitro. By means of IFN-dependent biological markers (e.g. beta-2-microglobulin, neopterin) clinically effective but atoxic doses of IFN-alpha could be defined for HCL and CML. In final conclusion, the recent studies on the clinical efficacy of IFN-alpha revealed its potent antitumoral effect in hematological malignancies. However, the further proof of the potential benefit of IFN treatment versus conventional therapeutic strategies remains to be elucidated.
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PMID:[Interferon-alpha in the treatment of hematologic neoplasms]. 352 22

It was the aim of this study to investigate the antileukemic activities of recombinant interferon beta (rIFN beta) in chronic-phase CML in vitro and in vivo. Nine patients in the early chronic-phase of CML were treated in a phase-II trial with escalating doses of rIFN beta. In parallel, antiproliferative and immunomodulatory activities of rIFN beta and rIFN alpha 2b were studied in vitro. rIFN beta exhibited a significantly higher antiproliferative activity on hematopoietic progenitor cells of CML patients in vitro than rIFN alpha 2b. In contrast, only very limited clinical antileukemic efficacy of rIFN beta was observed. None of the patients achieved a complete or partial hematologic response (0% response rate, 0-36% 95 C.I.). Primary resistance of CML patients to rIFN beta treatment was caused neither by antibody formation against the recombinant material nor by deficient IFN receptor targeting and/or signaling; Induction of serum levels of beta-2-microglobulin (beta-2-m) and neopterin after administration of rIFN beta was comparable to that seen after administration of rIFN alpha. However, rIFN beta treatment less effectively induced biosynthesis of interleukin-1 receptor antagonist protein (IL-1-Ra) than rIFN alpha 2b. Thus, we conclude that rIFN beta at doses up to 12 MU/day s.c. is ineffective for treatment of chronic-phase CML. Further investigations into divergent biologic responses to various type-I interferons might help to elucidate mechanisms crucial for IFN action in patients with CML.
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PMID:Divergent in vivo and in vitro antileukemic activity of recombinant interferon beta in patients with chronic-phase chronic myelogenous leukemia. 769 61

Serum neopterin (Np), beta 2-microglobulin (beta 2-M), and 2',5'-adenylate (2',5'A) levels and intracellular 2',5'A and human Mx (Hu-Mx) protein synthesis were measured in 20-24 chronic myeloid leukemia patients before and during 1 year of IFN-alpha treatment and in a further 8-9 patients before and at the end of the first and second treatment weeks only. Univariate analysis showed that IFN-alpha increased Np and 2',5'A serum levels and intracellular concentrations of 2',5'A and Hu-Mx significantly from the end of the first week to month 12 of therapy. The biologic marker profiles were similar in cytogenetic responders and nonresponders, as well as in patients treated with IFN-alpha early (< 12 months from diagnosis) or late (after > 12 months standard chemotherapy). Further, there were no differences in the short-term (first 14 days) or long-term (during 12 month therapy) induction of the biologic markers irrespective of whether IFN-alpha 2a or IFN-alpha 2b was given. Because multivariate analysis revealed no significant interactions between cytogenetic response, time to treatment, and type of IFN-alpha used, increments in intracellular 2',5'A and Hu-Mx protein were similar at all study times for all factor combinations tested. Np levels varied significantly only during the first 14 therapy days; changes in serum 2',5'A were never statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-alpha-induced biologic modifications in patients with chronic myelogenous leukemia. 789 54

IL-10 plays an important role in the control of immune reactions during systemic infection. Here, IL-10 serum levels were investigated in patients after BMT. The IL-10 levels correlated with the clinical course of the patients and with serum levels of C-reactive protein (CRP) and neopterin (NP). A total of 26 patients with AML (7), ALL (12), CML (2), NHL (3) and multifocal Ewing's sarcoma (2) had received autologous (10) or allogeneic (16) BMT from related (9) or unrelated donors (7). Routine serum samples were obtained prior to BMT and at days 46 and 100 after BMT. However, in patients with severe complications additional samples were drawn at individual points in time. Prior to BMT, IL-10 serum levels were not detectable in 24/24 patients. Post-BMT, 11 patients developed elevated IL-10 levels, of these eight died of complications (DOC), whereas only one of 15 patients with undetectable IL-10 died of complications, indicating that high IL-10 levels were significantly correlated with severe life-threatening complications (chi2, P < 0.01). To determine the pathomechanism and role of the increased IL-10 levels, they were correlated to the respective NP and CRP serum concentrations. CRP and NP concentrations were found significantly elevated in patients with detectable IL-10, indicating a severe acute phase reaction associated with macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associated with fatal outcome. Since IL-10 is a strong suppressor of T cell immunity, high IL-10 production in patients with severe complications such as septic shock or GVHD > grade II after BMT might lead to functional immunodeficiency contributing to the poor prognosis of these patients.
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PMID:High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation. 933 50

Urinary neopterin levels, blood dihydropteridine reductase activity as well as other frequently used clinical parameters were evaluated in 110 patients suffering from various types of lymphomas and leukemias. Among them neopterin was detected as the most sensitive marker representing the severity of malignancy (p<0.00001). All patients with active diseases had significantly raised urinary neopterin levels compared to those in remission and healthy controls. Of 69 patients with active disease 66 (96%) were above the upper limit seen in healthy subjects. In addition, the highest neopterin excretion was found in patients with active chronic myeloid leukemia (1469+/-479 micromol/mol creatinine n=16). In contrast, only 1 of 41 patients in stable responsive disease and remission (2.4%) had increased urinary neopterin levels above the upper limit. Dihydropteridine reductase (DHPR) activities were also detected in all patients and control groups. In active disease slightly reduced (DHPR) activities were evident (3.42+/-0.37 for controls, 2.92+/-0.39 in active disease and 3.28+/-0.42 nmol red cytochrome C/min/5 mm diameter disc in remission patients). However in patients under medication this was strengthened. This data also suggest that DHPR activity can be effected by chemotherapy. The results of the present study support the fact that urinary neopterin levels may be an useful and reliable early prognostic marker for neoplasia when used together with other prognostic indicators. Our data also suggest that reductions in DHPR activities may also be an underlying cause for the neurological disorders that are commonly seen in patients with haematological malignancies.
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PMID:Dihydropteridine reductase activity and neopterin levels in leukemias and lymphomas: is there any correlation between these two parameters? 1070 61

Among malignant diseases, chronic myeloid leukaemia (CML) is one of the best suited candidates for immunotherapy. For this purpose it is necessary to broaden the present knowledge on the immunology of this disease. As a part of such a project, the levels of kynurenine (KYN) and neopterin (NPT) were studied in 28 CML patients and in the same number of healthy subjects. At diagnosis, both KYN and NPT levels were found to be elevated in a significant portion of the patients and dependent on their leukocyte count. As in the case of KYN, increased NPT levels dropped after achieving remission. When correlating KYN and NPT levels with a selection of other markers tested, significant association was revealed only in the case of CRP and IL-6. However, there were several patients with increased KYN levels in whom NPT was not detected, and vice versa. The relapse of the disease observed in two patients was accompanied by an increased level of NPT in both cases, but by an increased level of KYN in only one of them. No significant correlation was found between KYN and NPT levels in sera taken at diagnosis. However, when the whole set of sera was taken into consideration, the association became statistically significant. Although the data obtained revealed a number of similarities between KYN and NPT production in CML patients, it also suggested a difference in the kinetics of these two biomarkers' production.
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PMID:The Relationship of Kynurenine and Neopterin Levels and Their Association with a Selection of Other Immune Markers in Chronic Myeloid Leukaemia Patients. 2818 46