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)

Apart from endothelial cells, the receptor tyrosine kinase TEK/Tie-2 is also expressed by primitive hematopoietic stem cells. While the role of this receptor and its ligand angiopoietin-1 (ang-1) during angiogenesis has been intensively studied before, little is known about their function in normal or malignant hematopoiesis. Recently several studies suggested that TEK plays an important role in the proliferation of primitive hematopoietic cells. We, therefore, analyzed blood cells of healthy donors and leukemia patients for expression of TEK and ang-1 by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. We found an increased expression of the receptor and its ligand in 11 of 17 cases of acute and chronic myeloid leukemia (CML) but not in four lymphocytic leukemias or five myeloid leukemias in remission. Abundant ang-1 message could also be detected in 4/6 myeloid and 1/9 cell lines of lymphocytic origin, but only one cell line co-expressed the TEK receptor, suggesting that ang-1 and TEK were probably expressed by different subsets of cells in the leukemic samples. Recently, several studies have indicated that angiogenic factors like ang-1 and vascular endothelial growth factor can enhance the proliferation of normal and malignant hematopoietic cells. The expression of both the TEK receptor and its ligand in acute myeloid leukemia (AML) and CML patients might, therefore, suggest an involvement of these genes in the pathogenesis of myeloproliferative disorders.
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PMID:Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia. 1175 66

When evaluating bone marrow sections for markers of neo-angiogenesis, we found that megakaryocytes stained markedly positive for cyclooxygenase-2 (Cox-2), Tie-2 and glycodelin. This apparently novel finding was further evaluated for disease-specific variations. Bone marrow sections from two patient groups, known to be characterized by clonal megakaryocytopoiesis, viz. chronic myeloid leukaemia and polycythaemia vera, stained, however, similarly to healthy marrows for these markers. The biochemical background and clinical significance of Cox-2, Tie-2 and glycodelin remains to be elucidated.
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PMID:Expression of cox-2, tie-2 and glycodelin by megakaryocytes in patients with chronic myeloid leukaemia and polycythaemia vera. 1271 75

Angiogenesis is a feature of hematological malignancies which may provide prognostic information. However, there is, as yet, no established marker for leukemia-associated vessels in bone marrow. In this study, immunohistochemical stainings for von Willebrand factor (vWf), CD34, Tie-2, angiomodulin, glycodelin, cycloxygenase-2 (Cox-2) and endoglin were compared in order to identify the bone marrow vasculature. Chronic myeloid leukemia (CML), a disease displaying intense angiogenesis, and polycythemia vera (PV), a disease with a low microvascular density (MVD), were studied, as well as normal bone marrow. Only vWf, CD34 and Tie-2 stained the bone marrow endothelium. Although more vessels were stained for vWf than for CD34, there was no evidence that vWf stained more disease-associated vessels. In double staining, Tie-2 co-localized with CD34, but vessels staining only for Tie-2 were also found. However, the number of Tie-2-positive vessels did not correlate to either the MVD or the disease. Angiomodulin, glycodelin, Cox-2 and endoglin did not stain vessel-like structures. In conclusion, estimating the MVD by means of CD34 staining appears to be the most reliable method, but none of the tested molecules qualified as a specific marker for leukemia-associated vessels in the bone marrow.
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PMID:Characterization of blood vessels in bone marrow from patients with chronic myeloid leukemia and polycythemia vera. 1551 21

The system involving angiopoietin-2 (Ang-2) and its receptor, Tie-2, appears to play an important role not only in tumor angiogenesis, but also in the biology of haematological and non-haematological malignancies. In the present study we evaluated the serum levels of soluble Ang-2 (sAng-2) and soluble Tie-2 (sTie-2) in patients with haematological malignancies. Measurements were carried out in 15 patients with chronic myeloid leukaemia (CML), 25 with essential thrombocythemia (ET), 24 with multiple myeloma (MM) and six with monoclonal gammopathy of undetermined significance (MGUS). In addition, we correlated the levels of angiopoietins with known prognostic factors. sAng-2 and sTie-2 were quantified with enzyme-linked immunosorbent assay (ELISA). In patients with CML and MM the levels of sAng-2 were significantly higher (1686.53 +/- 936.41 pg/mL and 1917.82 +/- 1427 pg/mL, respectively) than in controls (n = 15; 996.096 +/- 414.65 pg/mL) (P < 0.01). In patients with MM sAng-2 levels were significantly increased with increasing stage of disease, from stage I to stage III (P < 0.03) and presented a trend of correlation with Beta2-microglobulin levels (r = 0.317) and grade of bone involvement. Furthermore, the levels of sAng-2 determined after 6 months of chemotherapy in CML patients were significantly lower than at diagnosis in the patients who achieved haematological remission. Circulating sTie-2 levels were increased in patients with ET (17.5 +/- 9.2 vs 9 +/- 3.5 ng/mL; P < 0.01) and in those with CML (16.29 +/- 8.7 ng/mL; P < 0.04). In conclusion, abnormal levels of sAng-2 and sTie-2 are present in some haematological malignancies. These markers may play a role in the pathophysiology of these conditions and their progression.
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PMID:Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies. 1697 37

Tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with chronic myeloid leukemia (CML). However, patients with CML need to receive TKI therapy for several years. Hence, the safety of long-term TKI treatment warrants utmost attention. Among various adverse events caused by TKI therapy, cardiovascular events (CVEs), such as acute myocardial infarction, cerebral infarction, and pulmonary hypertension, are the most serious with high mortality. TKIs inhibit various off-target molecules involved in the occurrence of CVEs such as c-Kit, platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), and Tie-2/Tec. At present, nilotinib, dasatinib, and ponatinib, but not bosutinib, have been demonstrated to increase the risk of CVEs in patients with CML compared with imatinib. Conversely, patients with CML have also been shown to have high CVE risks regardless of the TKI treatment compared with non-cancer population. Hence, further analyses are required to deduce the influence of TKI treatment on CVEs. Whatever the cause may be, to prevent CVEs in patients with CML, we need to appropriately screen and monitor CVE risks such as hypertension, serum glucose, lipid levels, ankle-brachial index (ABI), Electrocardiography (ECG), and echocardiography before and during TKI treatment.
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PMID:[Management of cardiovascular complications in CML patients treated with tyrosine kinase inhibitors]. 2941 32