Dysregulated angiogenesis in B-chronic lymphocytic leukemia: Morphologic, immunohistochemical, and flow cytometric evidence

Frater, John L.; Kay, Neil E.; Goolsby, Charles L.; Crawford, Susan E.; Dewald, Gordon W.; Peterson, LoAnn

doi:10.1186/1746-1596-3-16

Cited by 49 publications

(57 citation statements)

References 34 publications

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“…62,63 To date, aberrant expression of HIF-1a and/or HIF-2a has been documented in cancers of the brain, colon, lung, breast, prostate, kidney, pancreas, cervix, bladder and ovary, [64][65][66][67][68][69] and overexpression of both HIFs has been found to indicate a highly aggressive disease phenotype associated with poor prognosis. [70][71][72][73][74][75][76] Whereas examination of aberrant HIF expression has largely been restricted to solid tumors, recent studies have reported that HIF-1a and HIF-2a are also overexpressed in hematological malignancies such as diffuse large B-cell lymphoma, 77,78 chronic lymphocytic leukemia 79 and acute lymphoblastic leukemia. 80 Although HIF-1a and HIF-2a show 48% amino-acid sequence homology and have similar protein structures and oxygendependent mechanisms of regulation, there are a growing number of physiological and mechanistic differences between these proteins, which indicates that they possess distinct, nonredundant roles.…”

Section: Hypoxia and Cancermentioning

confidence: 99%

The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma

et al. 2011

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Hypoxia is an imbalance between oxygen supply and demand, which deprives cells or tissues of sufficient oxygen. It is wellestablished that hypoxia triggers adaptive responses, which contribute to short-and long-term pathologies such as inflammation, cardiovascular disease and cancer. Induced by both microenvironmental hypoxia and genetic mutations, the elevated expression of the hypoxia-inducible transcription factor-1 (HIF-1) and HIF-2 is a key feature of many human cancers and has been shown to promote cellular processes, which facilitate tumor progression. In this review, we discuss the emerging role of hypoxia and the HIFs in the pathogenesis of multiple myeloma (MM), an incurable hematological malignancy of BM PCs, which reside within the hypoxic BM microenvironment. The need for current and future therapeutic interventions to target HIF-1 and HIF-2 in myeloma will also be discussed.

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Section: Hypoxia and Cancermentioning

confidence: 99%

The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma

et al. 2011

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“…17,18 Constitutive HIF-1a expression was suggested to induce vascular endothelial growth factor (VEGF) upregulation and neoangiogenesis. [19][20][21] However, because HIF-1a regulates a variety of other functions in solid tumors and hematologic malignancies, 1,22,23 we asked whether HIF-1a also controlled other aspects of CLL pathogenesis.…”

Section: Hif-1a Regulates Chemotaxis and Adhesion To Stroma In Cllmentioning

confidence: 99%

HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment

Valsecchi

Coltella

Belloni

et al. 2016

Blood

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“…The process of angiogenesis (new blood vessel formation from pre-existing vasculature) has been shown to be crucial for growth and metastasizing ability of solid tumors mainly by increasing the oxygen and nutrients supply to malignant cells [2]. Angiogenesis in "liquid" tumors was supposed to be less important, nevertheless numerous recent studies have shown enhanced angiogenesis in many hematological malignancies including chronic myeloid leukemia [3], acute myeloid leukemia [4], acute lymphocytic leukemia [5], and CLL [6][7][8]. It has been demonstrated that elevated markers of angiogenesis correlate with unfavorable prognosis of CLL [9][10][11].…”

mentioning

confidence: 99%

Prognostic relevance of angiopoietin-2, fibroblast growth factor-2 and endoglin mRNA expressions in chronic lymphocytic leukemia

Vrbacky¹,

Nekvindová²,

Řezáčová³

et al. 2014

neo

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Elevated levels of circulating angiogenic cytokines and increased expression of genes encoding angiogenic factors have been reported in recent years in patients with chronic lymphocytic leukemia (CLL) but data regarding prognostic and predictive significance are still limited. Therefore, in the present study based upon our prior pilot results, we measured mRNA expressions of angiopoietin-2 (Ang-2), fibroblast growth factor-2 (FGF-2) and endoglin (CD105) by reverse transcription quantitative PCR in purified CD19+ cells from 70 untreated CLL patients (median age, 63 years; males, 64%; Rai III/IV stages, 29 %; unmutated IgVH genes, 60 %) and evaluated their possible association with established prognostic factors and clinical course of the disease. Higher expression of Ang-2 was significantly associated with unmutated IgVH genes (n = 55, p = 0.003). Higher CD105 expression was significantly associated with unmutated IgVH genes (n = 55, p < 0.001), high CD38 expression (n = 66, p = 0.022), high ZAP-70 expression (n = 66, p = 0.010), Rai stage I-IV (n = 70, p < 0.001), progressive clinical course of CLL (n = 70, p = 0.001) and shorter time to treatment (n = 70; p < 0.001). Expression of FGF-2 was not significantly associated with any of the prognostic markers. These results indicate that elevated expression of Ang-2 and in particular CD105 by CLL cells is associated with unfavorable prognostic features and clinical outcome; thus, both cytokines appear to play an important role in biology and progression of CLL and warrant further investigation.

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Dysregulated angiogenesis in B-chronic lymphocytic leukemia: Morphologic, immunohistochemical, and flow cytometric evidence

Abstract: Background: The extent of enhanced bone marrow angiogenesis in chronic lymphocytic leukemia (CLL) and relationship to proangiogenic factors and prognostic indicators is largely unexplored.

Cited by 49 publications

References 34 publications

The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma

The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma

HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment

Prognostic relevance of angiopoietin-2, fibroblast growth factor-2 and endoglin mRNA expressions in chronic lymphocytic leukemia

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