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)

L-selectin is a glycoprotein which is one of three members in a family of cell adhesion molecules called selectins. L-selectin is present in distinct forms on both neutrophil granulocytes and lymphocytes, and it appears to play an important role in the early stages of leukocyte-endothelial cell interaction. Activation of leukocytes leads to shedding of the extracellular part of L-selectin which thus forms a soluble adhesion molecule, sL-selectin, which retains functional capacity and can be detected in serum. In the present study we have developed a specific, sensitive sandwich ELISA to measure the serum level of sL-selectin in patients with hematological and infectious disorders. Three patients with acute myeloid leukemia in remission and 1 patient with chronic myeloid leukemia in chronic phase were followed during bone marrow transplantation and the level of sL-selectin was found to correlate closely to the leukocyte counts with no detectable sL-selectin during periods of severe leukopenia. In 11 patients with chronic phase chronic myeloid leukemia and 13 patients with chronic lymphocytic leukemia the sL-selectin level was also found to correlate closely to the leukocyte count (R = 0.98; p = 0.001 and R = 0.83; p = 0.004 respectively). One CML patient with a leukocytosis of 385 x 10(9)/l was found to have an sL-selectin concentration 625 times above normal. Ten patients with acute pneumonia were evaluated at diagnosis and at the time of follow-up 4-8 weeks later. In all patients the initial sL-selectin level was higher than at follow-up. However, no close correlation between sL-selectin and leukocyte count or CRP (C-reactive protein) at the time of diagnosis was found. In summary, we have found that the sL-selectin level in human serum closely correlates to the leukocyte count in both CML and CLL and during bone marrow transplantation.
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PMID:Correlation between serum level of soluble L-selectin and leukocyte count in chronic myeloid and lymphocytic leukemia and during bone marrow transplantation. 769 Mar 31

Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 50 patients with plasma cell dyscrasias using a commercially available immunoenzymatic assay kit. There were 40 patients with multiple myeloma (MM), 5 patients with monoclonal gammopathy of undetermined significance (MGUS), 3 patients with solitary plasmacytoma (SPC), 1 patient with chronic myelogenous leukaemia and multiple myeloma (CML/MM), and 1 patient with plasma cell leukaemia (PCL). We found that serum sIL-6R concentrations were higher in MM patients (62.53 +/- 38.85 ng/ml) than in 20 normal volunteers studied (36.75 +/- 13.79 ng/ml) (p < 0.01). The cut-off value of 65 ng/ml seen in 2 of our controls was arbitrarily taken as the upper limit of the control range for serum sIL-6R; according to this criterion, 14 patients with MM (35%), 1 patient with SPC, the unique patient with CML + MM, and the unique patient with PCL had elevated concentrations of the receptor. Patients with MGUS had normal sIL-6R values. In MM patients, serum sIL-6R levels correlated with the clinical phase of the disease: they were elevated in patients with early or late active disease and ranged within normal limits in patients with plateau-phase disease (p < 0.001). Thirteen of 27 patients with active MM had elevated serum sIL-6R values, i.e. 48.1%, but only 1 out of 13 patients with disease in the plateau phase, i.e. 7.7% (p < 0.05). Furthermore, in the entire group of MM patients, serum sIL-6R levels correlated with the concentrations of serum beta 2-microglobulin, (p < 0.02), CRP (p < 0.01), ferritin (p < 0.01) and LDH (p < 0.01), while they did not correlate with disease stage, haemoglobin levels, proportion of marrow myeloma cells, the values of serum IL-6, the levels of serum albumin, or the grade of bone lesions. We conclude that elevated serum sIL-6R levels should be related to the growth of myeloma cells and suggest that serum sIL-6R concentrations may be used as an indicator of disease activity.
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PMID:Serum levels of soluble IL-6 receptor in multiple myeloma as indicator of disease activity. 915 60

After bone marrow transplantation, a prolonged dysregulation of humoral immunity, including restricted electrophoretic heterogeneity of serum immunoglobulins and the appearance of homogeneous immunoglobulin components, can be observed. The current study was undertaken to characterize further and define the posttransplantational incidence of monoclonal and oligoclonal immunoglobulins, as well as the clinical and laboratory correlations of these phenomena. For this purpose, serial serum protein (IgM, IgG, IgA and CRP) quantification, electrophoresis and immunofixation were performed on 29 patients undergoing allogeneic bone marrow transplantation for chronic myeloid leukemia. 23 out of the 29 patients developed transient oligoclonal and/or monoclonal gammopathies that appeared between 20 and 1750 posttransplantational days. No correlation, however, between the development of graft versus host disease, EBV or CMV infections, or any other symptoms and development of homogeneous immunoglobulin components was seen. Therefore, the development of oligoclonal and monoclonal gammopathies after bone marrow transplantation may be an ubiquitous finding reflecting the inadequacy, i.e. oligoclonality of the recovering B-cell system.
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PMID:[Restricted antibody diversity after bone marrow transplantation--homogeneous immunoglobulins]. 1124 20

In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broaden the present knowledge on the immune reactivity of CML patients. A group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papillomaviruses. To clearly discriminate between changes associated with the disease and those induced by the therapy, all patients were enrolled prior to the start of any anti-leukaemic therapy. Statistically significant differences between patients and controls were found in the levels of IgA, C4 component of complement, CRP and IL-6, the production of Th1 cytokines in stimulated CD3 cells and the E. coli stimulatory index. The analysis of the interrelationship between the results obtained in the individual patients presented some unexpected findings, such as the lack of correlation between the CRP and IL-6 levels. It will be the purpose of a follow-up to determine whether and how the immune status of the patients prior to the treatment correlates with their response to therapy and how the individual immunological profiles change in the course of the disease. These observations will be utilized in the future immunotherapeutic studies to constitute the vaccine- and placebo-treated groups.
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PMID:Immunological profiles of patients with chronic myeloid leukaemia. I. State before the start of treatment. 1708 15

Chronic myeloid leukemia (CML) accounts for 20% of all adult leukemias worldwide. Most Egyptian patients are diagnosed in the chronic phase and progress to the accelerated or blastic phase, which is related with decreased survival. Various pro-inflammatory cytokines are involved in the pathogenesis of chronic leukemia but their prognostic significance is unknown. The aim of the current study is to determine the validity of TNF-alpha, IL-6, IL-18 and CRP levels as prognostic markers in CML patients. These parameters were monitored with clinical routine tests in 25 CML patients besides ten healthy control subjects at National Cancer Institute, Cairo, Egypt. IL-6 and IL-18 levels before hydroxyurea treatment were significantly higher in all patients compared to controls (P<0.001 for both levels). At hematological remission, significant reductions were observed for IL-6 (P<0.001), IL-18 (P<0.001) and CRP (P<0.001) whereas reduction in the levels of TNF were non-significant. Moreover, an inverse correlation was observed between both of TNF (P<0.05) and CRP (p<0.01) on one side and megakaryocytic dysplasia on the other side. These findings offer evidence that TNF may have potential prognostic role in megakaryocytic dysplasia detection.
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PMID:Cytokine profiling as a prognostic markers in chronic myeloid leukemia patients. 2308 69

Tyrosine kinase inhibitors (TKI) such as imatinib, nilotinib and dasatinib are now established as highly effective frontline therapies for chronic myeloid leukaemia (CML). Disease control is achieved in the majority of patients and survival is excellent such that recent focus has been on toxicities of these agents. Cumulative data have reported an excess of serious vascular complications, including arterial thrombosis and peripheral arterial occlusive disease, in patients receiving nilotinib in comparison with other TKIs, with resultant interest in delineating the pathophysiology and implications for rationale cardiovascular risk modification. To address this issue, we studied the effects of imatinib, nilotinib and dasatinib on platelet function and thrombus formation in human and mouse models using in vitro, ex vivo and in vivo approaches. In vitro studies demonstrated that dasatinib and imatinib but not nilotinib inhibited ADP, CRP, and collagen-induced platelet aggregation and moreover, that nilotinib potentiated PAR-1-mediated alpha granule release. Pretreatment of wild-type C57BL/6 mice with nilotinib but not imatinib or dasatinib, significantly increased thrombus growth and stability, on type I collagen under ex vivo arterial flow conditions and increased thrombus growth and stability following FeCl3-induced vascular injury of mesenteric arterioles and carotid artery injury in vivo. Whole blood from nilotinib-treated CML patients, demonstrated increased platelet adhesion ex vivo under flow, increased plasma soluble P- and E-selectin, sICAM-1, sVCAM-1, TNF-alpha, IL-6 levels and endogenous thrombin potential (ETP) levels in vivo, despite being on daily low-dose aspirin. These results demonstrate that nilotinib can potentiate platelet and endothelial activation and platelet thrombus formation ex vivo and in vivo.
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PMID:The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state. 2749 73

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