Role of angiogenesis in chronic lymphocytic leukemia

Abstract

Angiogenesis is a physiologic process of new blood vessels formation mediated by various cytokines called angiogenic and angiostatic factors. Although its potential pathophysiologic role in solid tumors has been extensively studied for more than 3 decades, enhancement of angiogenesis in chronic lymphocytic leukemia (CLL) and other malignant hematological disorders has been recognized more recently.An increased level of angiogenesis has been documented by various experimental methods both in bone marrow and lymph nodes of patients with CLL. Although the role of angiogenesis in the pathophysiology of this disease remains to be fully elucidated, experimental data suggest that several angiogenic factors play a role in the disease progression. Biologic markers of angiogenesis were also shown to be of prognostic relevance in CLL. The current findings provide the rationale for investigating antiangiogenic agents in CLL. In the current review angiogenesis in CLL is discussed and its potential diagnostic and therapeutic applications. Cancer 2006;107:925-34.

Antagonism of the human epidermal growth factor receptor family controls disease severity in murine collagen‐induced arthritis

“…Angiogenesis is known to play a prominent role in several cancers, with involvement in metastasis and aberrant cell proliferation leading to tumor progression (9,24). The hyperplastic proliferating synovium in arthritis has pathophysiologic similarities to proliferating tumors, in terms of shared angiogenic mechanisms (23,25).…”

“…Several types of treatments are currently available, including steroids, biologic agents targeting TNF␣ or interleukin-1␤, and those targeting specific T cell markers, such as anti-CTLA-4 agents and agents targeting B cell involvement (4-7). There is a possible link between the formation of new blood vessels and destruction caused by matrix metalloproteinases, which may represent another important mechanism in the progression of several autoimmune diseases and cancers (8,9). There has been increasing acceptance of therapies aimed at abrogating signaling mediated through various members of the receptor tyrosine kinase (RTK) superfamily of cell surface receptors (10,11).…”

Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia

“…Direct cell-cell interactions as well as soluble factors might support tumor growth. [6][7][8][9] Prosurvival signals might be supported by the tumor necrosis factor (TNF) or some distinctive members of TNF family such as BAFF and APRIL as well as angiogenic factors VEGF. [6][7][8] By targeting not only leukemic cells but also the tumor microenvironment and by inhibiting angiogenesis, CLL might be more effectively treated.…”

Microenvironment Interactions in Chronic Lymphocytic Leukemia: A Delicate Equilibrium Linking the Quiescent and the Proliferative Pool

“…CLL B-cells can also express receptors for some of these pro-angiogenetic factors, including VEGF receptors VEGFR1 and 2 as well as the Ang-receptor. Signaling through these receptors significantly prolongs cell survival [41]. Additionally, it has been described that thioredoxin (Trx) is expressed in LN of CLL patients and that this expression can increase the CLL survival clone.…”