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

Ex vivo culture of CD34+ has the potential to provide large numbers of cells for clinical use in autologous and allogeneic transplantation and for experimental research involving genetic manipulation. We evaluated the ex vivo expansion of CD34+ cells obtained from bone marrow (BM) and peripheral blood (PB) of untreated patients with chronic myeloid leukaemia (CML) in the chronic phase and compared these results with those obtained from BM from normal volunteers (NBM) and peripheral blood after mobilising chemotherapy from patients with non-haematological disorders (MPB). Selected CD34+ cells were stimulated with interleukin 1(beta), interleukin IL-3, interleukin IL-6 and stem cell factor. The proliferation observed in patients with CML was similar to that seen in normal donors. CD34+ cells derived from patients with CML are more differentiated than their normal counterparts, as shown by the coexpression of CD34 and CD33 antigens on day 0 (85.6% for CML-BM and 76.8% for CML-PB). The culture conditions allowed a significant expansion of granulocyte-macrophage colony-forming units (CFU-GM) from NBM (33-fold increase) and MPB (22-fold increase), in contrast with CML-derived BM and PB CD34+ cells (2.3-fold increase). These results indicate that the optimal time to harvest ex vivo expanded cells is dependent on a critical compromise between cell numbers and successful retention of their repopulating potential.
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PMID:Ex vivo expansion and characterisation of CD34+ cells derived from chronic myeloid leukaemia bone marrow and peripheral blood, and from normal bone marrow and mobilised peripheral blood. 1099 28

Clonal thrombocytosis (CT) associated with myeloproliferative disorders (MPD) is believed to be secondary to autonomous unregulated platelet production. Secondary or reactive thrombocytosis (RT) can be observed in a number of clinical circumstances and may be related to persistent production of some thrombopoietic factors acting on megakaryocytes (MK). The goal of this study is to assess the serum concentrations of these cytokines in control subjects and patients with MPD associated with thrombocythemia, RT, and autoimmune thrombocytopenic purpura (ATP). Eleven patients with MPD, five with chronic myeloid leukemia (CML), three with polycythemia vera (PCV), two with essential thrombocythemia (ET), one with myelofibrosis, 15 with RT, eight with ATP, and 12 healthy volunteers were enrolled in the study. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF), fibronectin, intracellular adhesion molecule-1 (ICAM-1), and thrombomodulin (TM) were measured in these groups. Interleukin- 1beta, IL-6, and TNF levels were high in patients with RT and ATP, suggesting that these cytokines act on early uncommitted progenitors, promoting commitment along the MK lineage and leading to thrombocytosis or compensation for thrombocytopenia. TM was significantly increased in patients with MPD compared to all other groups, probably indicating the presence of subclinical endothelial damage. Fibronectin levels were high in MPD and RT patients. This finding can be secondary to high platelet turnover in these patients. We found that ICAM-1 levels were high in patients with clonal thrombocytosis. ICAM-1 can be one of the factors initiating the events ultimately leading to clonal thrombocytosis. Thrombocythemia associated with MPD is an autonomous phenomenon not regulated by cytokines.
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PMID:Cytokines, endothelium, and adhesive molecules in pathologic thrombopoiesis. 1129 90

Endogenous cytokines are aberrantly produced in many cancers, and serve as autocrine growth factors or indicators in immune response to the tumors. Hence, cytokine deregulation is likely to participate in the development or evolution of the malignant process. Over the last few years, endogenous cytokine levels have been correlated with phenotypic manifestations of cancer and with prognosis. For instance, serum IL-6 levels are elevated in both relapsed and newly-diagnosed Hodgkin's and non-Hodgkin's lymphoma, and these levels correlate with established prognostic features. Furthermore, in diffuse large cell lymphoma, serum IL-6 level is an independent prognostic variable for both complete remission and failure-free survival. Serum IL-10 levels are also elevated in lymphoid malignancies and predict outcome. In some cases, it may be that the balance between endogenous cytokine agonists and antagonists is disrupted. For instance, in chronic myelogenous leukemia, high cellular (leukocyte) levels of IL-1 beta and low levels of IL-1 receptor antagonist (IL-1RA) are seen in advanced disease and correlate with reduced survival. The molecular mechanisms underlying cytokine deregulation are now being investigated, with preliminary data suggesting heterogeneous genetic driving forces, including oncogene aberrations and viral infection.
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PMID:Cytokine deregulation in cancer. 1176 63

Chronic myeloid leukaemia (CML) dendritic cells (DC) are possible candidates for inducing antileukaemic immunity. This study aimed to investigate the frequency, phenotype and function of blood-derived leukaemic DC in comparison with DC from healthy donors using flow cytometric assays and mixed leucocyte reaction (MLR). Immature leukaemic DC displayed a reduced endocytotic capacity as compared with healthy controls. Moreover, in vitro maturation of leukaemic DC was found to be deficient. Expression of CD80, CD83, CD86, and major histocompatibility complex class I and class II antigens were reduced on lipopolysaccharide (LPS)-matured leukaemic DC but were enhanced by a mixture of interleukin 1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Upon stimulation with bacterial LPS, intracellular TNF-alpha and IL-8 production was diminished in maturing DC from CML patients. This distinct cytokine deficiency was overcome when leukaemic DC were stimulated with cytokines/PGE2. MLR showed fully functional leukaemic DC after TNF-alpha-induced maturation, but a reduced proliferative alloresponse of leukaemic peripheral blood mononuclear cells. Further, intracellular production of cytokines in CML-derived T cells was markedly reduced. These data indicated that, in CML, the maturation response of leukaemic monocyte-derived DC to a natural stimulus like LPS is abnormal and may be caused by an aberrant TNF-alpha response in these cells. Thus, TNF-alpha alone or in combination with pro-inflammatory and T-cell stimulatory cytokines should be considered as an adjuvant for DC-based immunotherapy in CML.
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PMID:Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia. 1249 78

Imatinib is a tyrosine kinase inhibitor that has been reported to specifically inhibit the growth of bcr-abl expressing chronic myeloid leukaemia progenitors. This drug functions by blocking the ATP-binding site of the kinase domain of bcr-abl, and has also been found to inhibit the c-abl, platelet-derived growth factor receptor, ARG and stem cell factor receptor tyrosine kinases. Reports have recently emerged demonstrating that imatinib also inhibits the growth of non-malignant haemopoietic cells. Here, we demonstrate that concentrations of imatinib within the therapeutic dose range inhibit the function of cultured monocytes (CM) from normal donors. A decrease in the response of CM to LPS was observed morphologically and functionally, with CM grown in the presence of imatinib showing decreased pseudopodia formation and inhibition of IL-6 and TNF-alpha production following LPS stimulation. Imatinib also reduced the ability of M-CSF and GM-CSF stimulated CM to phagocytose zymosan particles, with uptake of non-opsonized zymosan by M-CSF stimulated CM (M-CM) being most affected. M-CM that had been cultured in the presence of imatinib were also impaired in their ability to stimulate responder cells in a mixed lymphocyte reaction. These results demonstrate that human monocytes cultured in the presence of imatinib are functionally impaired, and suggest that imatinib displays inhibitory activity against other kinase(s) that play a role in monocyte/macrophage development.
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PMID:Imatinib inhibits the functional capacity of cultured human monocytes. 1566 Oct 41

A number of growth factors are involved in clonal haematopoietic expansion and their clinical significance in patients with chronic myeloproliferative diseases requires further evaluation. Using enzyme-linked immunosorbent assays, we analysed serum levels of interleukin (IL)-1a, IL-1b, IL-2, IL-6, the soluble IL-2 receptor alpha (sIL-2Ra), and thrombopoietin (TPO), in 25 individuals with myelofibrosis with myeloid metaplasia (MMM), 40 with essential thrombocythaemia (ET), eight with polycythaemia vera (PV), 10 patients with chronic myeloid leukaemia (CML) and 27 normal controls. These were correlated with clinicopathological characteristics including overall survival, and histopathological bone marrow features, including angiogenesis. The serum derived from patients with MMM, ET, PV and CML contained significantly higher IL-2 and sIL-2Ra than healthy subjects, while IL-6 levels were higher only in MMM and CML than controls. IL-2, sIL-2Ra and IL-6 levels were raised during the transformation phase of CML, during progression of MMM to AML, and ET and PV to myelofibrosis (P < 0.001). There was a positive correlation between IL-2, sIL-2Ra, IL-6 and angiogenesis in bone marrow samples. Cytokines may be useful markers for predicting clinical evolution, reflecting increased angiogenesis. This requires further evaluation to guide diagnostic and therapeutic options.
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PMID:Serum interleukin (IL)-1, IL-2, sIL-2Ra, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseases. 1611 26

An 80-year-old man presented to the internist with fever, fatigue and leukocytosis up to 66.8 x 10(3)/microl. Although a chronic myelogenous leukemia was initially suspected, he was diagnosed as metastatic bone marrow tumor with bone marrow necrosis from primary prostate cancer on the basis of the clinical and pathological findings. The serum concentrations of IL-6 and TNF-alpha were mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that these humoral factors were partially responsible for the leukemoid reaction although other factors induced by the bone marrow necrosis with bone marrow metastasis of prostate cancer are also likely involved.
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PMID:Leukemoid reaction in association with bone marrow necrosis due to metastatic prostate cancer. 1629 25

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

Keeping in view the fact that a single acquired genetic abnormality "Bcr-Abl chimeric gene" accompanied by elevated telomerase activity has been widely recognized to be responsible for the leukemic myelopoiesis observed in chronic myeloid leukemia (CML), the present study was addressed to understand as to how selective and specific knock-down of human telomerase reverse transcriptase (hTERT) gene within mononuclear cells derived from untreated CML subjects could influence the apoptotic, genotypic (such as Bcr-Abl; C-myc; Bcl-2; IL-6; GMCSF; IL-3; and acetylated H(3) and H(4)), and phenotypic (such as CD34 and CD89) characteristics of these cells. Based upon these results, we propose that hTERT gene-based drug design may be useful in the treatment of leukemic myelopoiesis.
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PMID:Functional genomics of hTERT gene in leukemic myelopoiesis. 1840 31

Chronic myeloid leukemia (CML) is a malignant disease of heampoitic stem cell resulting from clonal expansion of leukemic myeloid cells. Survivin is a recently identified member of the inhibitor of apoptosis protein family. The aim of the work is to analyze the expression of survivin in CML patient in chronic, accelerated and blastic phases and its correlation with other prognostic markers. The study included 50 CML patients (24 females and 26 males) and 10 healthy individuals (4 female and 6 male) as a control group. The studied groups were classified into group (I), 10 healthy individuals as a control group, group (II), 20 CML patients in chronic phase, Group (III), 15 CML patients in accelerated phase and Group (IV), 15 CML patients in blastic phase. The groups were subjected to clinical history and examination, CBC, ESR, BM aspiration (only patients), determination of serum survivin, IL-6 and beta2M levels by ELISA and survivin gene expression by quantitative real time PCR. There was a significant increase of survivin expression in patients as compared to controls (p < 0.001). The accelerated and blastic phases of the disease showed the highest significance (p < 0.001) than the chronic phase. Serum markers; survivin, IL6 and beta2M showed significant increase in the blastic phase, accelerated phase and chronic phase (p < 0.001, p < 0.001 and p < 0.001) respectively. A significant positive correlation was found between level of survivin expression and the other prognostic markers; high leucocytic count (r = 0.52), high peripheral basophile count (r= 0.81) and high peripheral blast cell count (r = 0.66), high level of serum survivin (r = 0.87), beta2 M (r = 0.76) and IL-6 (r= 0.90). On the other hand, a significant negative correlation was found between the survivin expression and hemoglobin concentration (r = 0.50). In conclusion, survivin is expressed in most cases of CML patients and its over expression is associated with bad prognosis.
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PMID:Molecular detection of survivin expression, antiapoptotic gene, and other prognostic markers, how they are correlated and how it could be of prognostic value in chronic myeloid leukemia patient. 2030 57


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