Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia

Müller, Anke; Lange, Karin de; Gaiser, Timo; Hofmann, Manfred; Bartels, H.; Feller, Alfred C.; Merz, Hartmut

doi:10.1016/s0145-2126(01)00110-2

Cited by 49 publications

(34 citation statements)

References 21 publications

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“…Indeed, angiopoietin signaling in AML most likely comprises paracrine, autocrine and, eventually, even intracrine (internal autocrine) loops. There is growing evidence that AML blasts also express the angiopoietin receptor Tie2 23,24,34 and establish an autocrine angiopoietin/Tie2 loop, 35 as already demonstrated for VEGF 9,36 or bFGF. 10 At least in endothelial cells, Ang-2 has also been shown to act through an internal autocrine (intracrine) loop.…”

Section: Discussionmentioning

confidence: 77%

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

et al. 2007

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Angiogenesis plays an important role in solid tumors and hematologic malignancies. The angiopoietins act as essential regulators in this process. We investigated the impact of circulating angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble Tie2 (sTie2) on overall survival in patients with acute myeloid leukemia (AML). Ang-1, Ang-2 and sTie2 were measured in plasma samples from 68 AML patients and 11 controls using enzyme-linked immunosorbent assay. Circulating levels of Ang-2 and sTie2 (median (range): 1098.0 (361.4-4147.6) pg/ml and 3.40 (1.21-10.00) ng/ml, respectively) were significantly elevated in AML patients as compared to controls (307.9 (199.7-1225.0) pg/ml and 2.88 (1.71-3.29) ng/ml; Po0.001 and P ¼ 0.014). In a univariate Cox proportional hazards model, higher levels of Ang-2 and sTie2 were predictive of poor survival. In multivariate analyses, Ang-2 and cytogenetics proved to be independent prognostic factors, with a relative risk of 4.07 (95% confidence interval (CI) 1.88-8.81) and 2.70 (95% CI 1.25-5.81), respectively. The 3-year survival rate for AML patients with Ang-2 levelsX1495.6 pg/ml was only 14.7% compared to 64.7% for those with Ang-2 levelso1495.6 pg/ml. These data provide evidence that circulating Ang-2 represents an independent prognostic factor in AML and may be used as a prognostic tool in the risk-adapted management of AML.

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Section: Discussionmentioning

confidence: 77%

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

et al. 2007

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“…As angiopoietin signaling in AML most likely compromise paracine, autocrine and eventually intracine loops. There is growing evidences that AML blasts express the angiopoietin-2 and receptors Tie-2 [14,15], and established Angiopoietin/Tie-2 loop. The soluble Tie-2 receptor compete with the cellular Tie receptor for interaction with Angi-2 leading to down regulation of the effect of Angi-2 on AML cells.…”

Section: Discussionmentioning

confidence: 99%

Soluble angiopoietin-2/sTie2 receptor ratio is an independent prognostic marker in adult acute myeloid leukemia

Aref

Menshawy

Azmy

et al. 2009

Indian J Hematol Blood Transfus

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Aim Angiogenesis is the formation of new blood vessels from preexisting one. The angiopoietins act a central role in these process. The aim of the present study is to the assess the impact of the circulating levels of angiopoietin-1 (Angi-1), Angiopoietin-2 (Angi-2), soluble Tie2 receptor (sTie2), and calculated Angi-2/sTie2 ratio on overall survival in 71 acute myeloid leukemia patients and 19 normal controls.Materials and methods Ang-2, and calculated angi-2/sTie values were signifi cantly higher in AML patients as compared to healthy volunteer ( P= 0.002, 0.015 respectively) on the other hand Angi-1 was not signifi cantly different in patients and control.Results In univariate Cox proportional hazards model Angi-2, sTie2, angi-2/sTie2 ratio were predictive of poor survival. In multivariate analysis the calculated angi-2/ sTie2 ratio is independent prognostic factor, with relative risk of 3.939, with 95% confi dence interval 0.002-0.001. ConclusionThe calculated angiopoietin-2/sTie2 ratio represent an independent prognostic factor in AML and its value should be considered when considering anti angiogenic therapy.

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“…A number of angiogenic cytokines have been identified in CML cells, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin‐1 (Ang‐1) and matrix metalloproteinases (MMP) 21, 22, 23, 51, 52, 53, 54. In addition, hepatocyte growth factor (HGF) is expressed in CML cells (Figure 2).…”

Section: Basophils As Unique Source Of Microenvironment‐remodelling Smentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

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Chronic myeloid leukaemia (CML) is a hematopoietic neoplasm defined by the chromosome translocation t(9;22) and the related oncogene, BCR‐ABL1. In most patients, leukaemic cells can be kept under control using BCR‐ABL1‐targeting drugs. However, many patients relapse which remains a clinical challenge. In particular, patients with advanced (accelerated or blast phase) CML have a poor prognosis. So far, little is known about molecular and cellular interactions and features that contribute to disease progression and drug resistance in CML. One key prognostic factor at diagnosis is marked basophilia. However, although basophils are well‐known multifunctional effector cells, their impact in CML remains uncertain. In this article, we discuss the potential role of basophils as active contributors to disease evolution and progression in CML. In particular, basophils serve as a unique source of inflammatory, angiogenic and fibrogenic molecules, such as vascular endothelial growth factor or hepatocyte growth factor. In addition, basophils provide vasoactive substances, like histamine as well as the cytokine‐degrading enzyme dipeptidyl‐peptidase IV which may promote stem cell mobilization and the extramedullary spread of stem and progenitor cells. Finally, basophils may produce autocrine growth factors for myeloid cells. Understanding the role of basophils in CML evolution and progression may support the development of more effective treatment concepts.

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Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia

Cited by 49 publications

References 21 publications

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

Soluble angiopoietin-2/sTie2 receptor ratio is an independent prognostic marker in adult acute myeloid leukemia

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

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Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia

Cited by 49 publications

References 21 publications

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

Soluble angiopoietin-2/sTie2 receptor ratio is an independent prognostic marker in adult acute myeloid leukemia

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

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The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia