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García-Pardo et al. J Cancer Metastasis Treat 2021;7:62 Journal of Cancer
DOI: 10.20517/2394-4722.2021.103
Metastasis and Treatment

Review Open Access

Regulation and function of angiogenic factors in
chronic lymphocytic leukemia

Angeles García-Pardo, Javier Redondo-Muñoz

Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de
Investigaciones Científicas, Madrid 280140, Spain.
Correspondence to: Dr. Angeles García-Pardo, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de
Investigaciones Científicas, Ramiro de Maeztu 9, Madrid 28040, Spain. E-mail: gelivejer@gmail.com; Dr. Javier Redondo-Muñoz,
Department of Molecular Biomedicine, Centro de Investigaciones Biológicas Margarita Salas, Ramiro de Maeztu 9, Madrid
28040, Spain. E-mail: javier.redondo@cib.csic.es
How to cite this article: García-Pardo A, Redondo-Muñoz J. Regulation and function of angiogenic factors in chronic lymphocytic
leukemia. J Cancer Metastasis Treat 2021;7:62. https://dx.doi.org/10.20517/2394-4722.2021.103

Received: 28 Apr 2021 First Decision: 9 Jul 2021 Revised: 16 Jul 2021 Accepted: 18 Oct 2021 Published: 5 Nov 2021
Academic Editors: Lucio Miele, Ribatti Domenico, Dominique Bonnet Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue
Zhang

Abstract
Progression of chronic lymphocytic leukemia (CLL) is determined by the localization of malignant cells in lymphoid
tissues, where they receive growth and survival signals. CLL cells produce angiogenic factors that are regulated by
internal and external stimuli and whose levels vary according to the clinical stage of the disease. Stromal cellular
and molecular components in CLL niches disturb the balance of pro- and antiangiogenic molecules in CLL cells and
induce an angiogenic switch. Additionally, CLL cells also influence the behavior of microenvironmental cells,
inducing endothelial cell proliferation and increasing the angiogenic capacity of macrophages, neutrophils, and
other cells present in CLL niches. As a result of these reciprocal functional interactions, bone marrow angiogenesis
is frequently increased in CLL and has been proposed as a prognostic marker in early disease. Besides their role in
regulating angiogenesis, angiogenic factors are also involved in CLL cell migration and survival, all contributing to
disease progression. Angiogenic factors, particularly vascular endothelial growth factor, have therefore been
attractive therapeutic targets in CLL and many clinical trials were established in the past years. However, the
results of these trials reveal that anti-angiogenic therapies alone are not as efficient as expected and should rather
be used in combination with other treatments.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
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