REFERENCES
1. Zenz T, Mertens D, Küppers R, Döhner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 2010;10:37-50.
2. Gaidano G, Foà R, Dalla-Favera R. Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest 2012;122:3432-8.
4. Delgado J, Nadeu F, Colomer D, Campo E. Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies. Haematologica 2020;105:2205-17.
5. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood 1975;46:219-34.
6. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981;48:198-206.
7. Eichhorst B, Robak T, Montserrat E, et al. ESMO Guidelines Committee. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021;32:23-33.
8. Fürstenau M, Eichhorst B. Novel agents in chronic lymphocytic leukemia: new combination therapies and strategies to overcome resistance. Cancers (Basel) 2021;13:1336.
9. Seifert M, Sellmann L, Bloehdorn J, et al. Cellular origin and pathophysiology of chronic lymphocytic leukemia. J Exp Med 2012;209:2183-98.
10. Bulian P, Shanafelt TD, Fegan C, et al. CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia. J Clin Oncol 2014;32:897-904.
11. Burgler S. Role of CD38 expression in diagnosis and pathogenesis of chronic lymphocytic leukemia and its potential as therapeutic target. Crit Rev Immunol 2015;35:417-32.
12. Puente XS, Pinyol M, Quesada V, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011;475:101-5.
13. Benedetti D, Tissino E, Pozzo F, et al. NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: link between the NOTCH1 and the NF-κB pathways. Leukemia 2018;32:654-62.
14. Davids MS, Burger JA. Cell trafficking in chronic lymphocytic leukemia. Open J Hematol 2012;3:1.
15. Redondo-Muñoz J, García-Pardo A, Teixidó J. Molecular players in hematologic tumor cell trafficking. Front Immunol 2019;10:156.
16. Malavasi F, Deaglio S, Damle R, Cutrona G, Ferrarini M, Chiorazzi N. CD38 and chronic lymphocytic leukemia: a decade later. Blood 2011;118:3470-8.
17. Gutjahr JC, Greil R, Hartmann TN. The role of CD44 in the pathophysiology of chronic lymphocytic leukemia. Front Immunol 2015;6:177.
18. Burger JA, Gribben JG. The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: insight into disease biology and new targeted therapies. Semin Cancer Biol 2014;24:71-81.
19. Aguayo A, Kantarjian H, Manshouri T, et al. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000;96:2240-5.
20. Shanafelt TD, Kay NE. The clinical and biologic importance of neovascularization and angiogenic signaling pathways in chronic lymphocytic leukemia. Semin Oncol 2006;33:174-85.
21. Letilovic T, Vrhovac R, Verstovsek S, Jaksic B, Ferrajoli A. Role of angiogenesis in chronic lymphocytic leukemia. Cancer 2006;107:925-34.
22. Kini AR, Kay NE, Peterson LC. Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia. Leukemia 2000;14:1414-8.
23. Peterson L, Kini AR. Angiogenesis is increased in B-cell chronic lymphocytic leukemia. Blood 2001;97:2529.
24. Frater JL, Kay NE, Goolsby CL, Crawford SE, Dewald GW, Peterson LC. Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence. Diagn Pathol 2008;3:16.
25. Negaard HF, Iversen N, Bowitz-Lothe IM, et al. Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors. Leukemia 2009;23:162-9.
26. Molica S, Vacca A, Ribatti D, et al. Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia. Blood 2002;100:3344-51.
27. Molica S, Cutrona G, Vitelli G, et al. Markers of increased angiogenesis and their correlation with biological parameters identifying high-risk patients in early B-cell chronic lymphocytic leukemia. Leuk Res 2007;31:1575-8.
28. Ding W, Nowakowski GS, Knox TR, et al. Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression. Br J Haematol 2009;147:471-83.
29. Attekum MH, Eldering E, Kater AP. Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk. Haematologica 2017;102:1469-76.
30. Dubois N, Crompot E, Meuleman N, Bron D, Lagneaux L, Stamatopoulos B. Importance of crosstalk between chronic lymphocytic leukemia cells and the stromal microenvironment: direct contact, soluble factors, and extracellular vesicles. Front Oncol 2020;10:1422.
31. Kay NE, Shanafelt TD, Strege AK, Lee YK, Bone ND, Raza A. Bone biopsy derived marrow stromal elements rescue chronic lymphocytic leukemia B-cells from spontaneous and drug induced cell death and facilitates an "angiogenic switch". Leuk Res 2007;31:899-906.
32. Edelmann J, Klein-Hitpass L, Carpinteiro A, et al. Bone marrow fibroblasts induce expression of PI3K/NF-kappaB pathway genes and a pro-angiogenic phenotype in CLL cells. Leuk Res 2008;32:1565-72.
33. Maffei R, Fiorcari S, Bulgarelli J, et al. Physical contact with endothelial cells through β1- and β2- integrins rescues chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis and induces a peculiar gene expression profile in leukemic cells. Haematologica 2012;97:952-60.
34. Xia Y, Lu RN, Li J. Angiogenic factors in chronic lymphocytic leukemia. Leuk Res 2012;36:1211-7.
35. Aguirre Palma LM, Gehrke I, Kreuzer KA. Angiogenic factors in chronic lymphocytic leukaemia (CLL): where do we stand? Crit Rev Oncol Hematol 2015;93:225-36.
36. Kay NE, Bone ND, Tschumper RC, et al. B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules. Leukemia 2002;16:911-9.
37. Baban D, Murray J, Earl H, Kerr D, Seymour L. Quantitative analysis of vascular endothelial growth factor expression in chronic lymphocytic leukaemia. Int J Oncol ;1996:8:29-34.
38. Chen H, Treweeke AT, West DC, et al. In vitro and in vivo production of vascular endothelial growth factor by chronic lymphocytic leukemia cells. Blood 2000;96:3181-7.
39. Ho CL, Hsu LF, Phyliky RL, Li CY. Autocrine expression of platelet-derived growth factor B in B cell chronic lymphocytic leukemia. Acta Haematol 2005;114:133-40.
40. Bauvois B, Dumont J, Mathiot C, Kolb JP. Production of matrix metalloproteinase-9 in early stage B-CLL: suppression by interferons. Leukemia 2002;16:791-8.
41. Kamiguti AS, Lee ES, Till KJ, et al. The role of matrix metalloproteinase 9 in the pathogenesis of chronic lymphocytic leukaemia. Br J Haematol 2004;125:128-40.
42. Redondo-Muñoz J, Escobar-Díaz E, Samaniego R, Terol MJ, García-Marco JA, García-Pardo A. MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by alpha4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration. Blood 2006;108:3143-51.
43. Duensing S, Atzpodien J. Increased intracellular and plasma levels of basic fibroblast growth factor in B-cell chronic lymphocytic leukemia. Blood 1995;85:1978-80.
44. Menzel T, Rahman Z, Calleja E, et al. Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood 1996;87:1056-63.
45. Gora-Tybor J, Blonski JZ, Robak T. Circulating proangiogenic cytokines and angiogenesis inhibitor endostatin in untreated patients with chronic lymphocytic leukemia. Mediators Inflamm 2003;12:167-71.
46. Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond) 2005;109:227-41.
47. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006;7:359-71.
48. Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2011;2:1097-105.
50. Molica S, Vitelli G, Levato D, Gandolfo GM, Liso V. Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia. Br J Haematol 1999;107:605-10.
51. Molica S, Vitelli G, Levato D, Ricciotti A, Digiesi G. Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia. Br J Cancer 2002;86:31-5.
52. Ding W, Knox TR, Tschumper RC, et al. Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia: implications for an angiogenic switch. Blood 2010;116:2984-93.
53. Maffei R, Marasca R, Martinelli S, et al. Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status. Leukemia 2007;21:1312-5.
54. Maffei R, Martinelli S, Santachiara R, et al. Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia. Blood 2010;116:584-92.
55. Vrbacky F, Smolej L, Vroblova V, et al. Angiopoietin-2 mRNA expression is increased in chronic lymphocytic leukemia patients with poor prognostic features. Hematology 2010;15:210-4.
56. Molica S, Vitelli G, Levato D, et al. Increased serum levels of matrix metalloproteinase-9 predict clinical outcome of patients with early B-cell chronic lymphocytic leukaemia. Eur J Haematol 2003;70:373-8.
57. Gusella M, Bolzonella C, Paolini R, et al. Plasma matrix metalloprotease 9 correlates with blood lymphocytosis, leukemic cell invasiveness, and prognosis in B-cell chronic lymphocytic leukemia. Tumour Biol 2017;39:1010428317694325.
58. Lopez-Dee Z, Pidcock K, Gutierrez LS. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm 2011;2011:296069.
59. Rosenwald A, Alizadeh AA, Widhopf G, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001;194:1639-47.
60. Sinha S, Boysen J, Nelson M, et al. Axl activates fibroblast growth factor receptor pathway to potentiate survival signals in B-cell chronic lymphocytic leukemia cells. Leukemia 2016;30:1431-6.
61. Ferrajoli A, Manshouri T, Estrov Z, et al. High levels of vascular endothelial growth factor receptor-2 correlate with shortened survival in chronic lymphocytic leukemia. Clin Cancer Res 2001;7:795-9.
62. Bairey O, Boycov O, Kaganovsky E, Zimra Y, Shaklai M, Rabizadeh E. All three receptors for vascular endothelial growth factor (VEGF) are expressed on B-chronic lymphocytic leukemia (CLL) cells. Leuk Res 2004;28:243-8.
63. Nowakowski GS, Mukhopadhyay D, Wu X, Kay NE. Neuropilin-1 is expressed by chronic lymphocytic leukemia B cells. Leuk Res 2008;32:1634-6.
64. Piechnik A, Dmoszynska A, Omiotek M, et al. The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients. Int J Cancer 2013;133:1489-96.
65. Gutiérrez-González A, Aguilera-Montilla N, Ugarte-Berzal E, et al. α4β1 integrin associates with VEGFR2 in CLL cells and contributes to VEGF binding and intracellular signaling. Blood Adv 2019;3:2144-8.
66. Saharinen P, Jeltsch M, Santoyo MM, Leppänen V, Alitalo K. The TIE receptor family. In: Wheeler DL, Yarden Y, editors. Receptor tyrosine kinases: family and subfamilies. Cham: Springer International Publishing; 2015. p. 743-75.
67. Aguayo A, Manshouri T, O'brien S, et al. Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL). Leuk Res 2001;25:279-85.
68. Palma LM, Flamme H, Gerke I, Kreuzer KA. Angiopoietins modulate survival, migration, and the components of the Ang-Tie2 pathway of chronic lymphocytic leukaemia (CLL) cells in vitro. Cancer Microenviron 2016;9:13-26.
69. Pötzsch B, Gehrke I, Poll-Wolbeck S, Flamme H, Kreuzer KA. Angiopoietin-2/Tie2 signaling in the microenvironment of chronic lymphocytic leukemia (CLL). Res Cancer Tumor 2014;3:6-18.
70. Maffei R, Fiorcari S, Martinelli S, et al. Angiopoietin-2 acts as a survival factor for chronic lymphocytic leukemia B cells throughout Tie-2 receptor engagement. Hematol Oncol 2018;36:372-5.
71. Bogdanovic E, Nguyen VP, Dumont DJ. Activation of Tie2 by angiopoietin-1 and angiopoietin-2 results in their release and receptor internalization. J Cell Sci 2006;119:3551-60.
72. Rutella S, Rumi C, Puggioni P, Barberi, Di Mario A, et al. Expression of thrombospondin receptor (CD36) in B-cell chronic lymphocytic leukemia as an indicator of tumor cell dissemination. Haematologica 1999;84:419-24.
73. Mateo V, Lagneaux L, Bron D, et al. CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia. Nat Med 1999;5:1277-84.
74. Mateo V, Brown EJ, Biron G, et al. Mechanisms of CD47-induced caspase-independent cell death in normal and leukemic cells: link between phosphatidylserine exposure and cytoskeleton organization. Blood 2002;100:2882-90.
75. Redondo-Muñoz J, Ugarte-Berzal E, García-Marco JA, et al. Alpha4beta1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells. Blood 2008;112:169-78.
76. Amigo-Jiménez I, Bailón E, Ugarte-Berzal E, Aguilera-Montilla N, García-Marco JA, García-Pardo A. Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide. PLoS One 2014;9:e99993.
77. Bailón E, Ugarte-Berzal E, Amigo-Jiménez I, et al. Overexpression of progelatinase B/proMMP-9 affects migration regulatory pathways and impairs chronic lymphocytic leukemia cell homing to bone marrow and spleen. J Leukoc Biol 2014;96:185-99.
78. Aguilera-Montilla N, Bailón E, Uceda-Castro R, et al. MMP-9 affects gene expression in chronic lymphocytic leukemia revealing CD99 as an MMP-9 target and a novel partner in malignant cell migration/arrest. Oncogene 2019;38:4605-19.
79. Aguilera-Montilla N, Bailón E, Ugarte-Berzal E, et al. Matrix metalloproteinase-9 induces a pro-angiogenic profile in chronic lymphocytic leukemia cells. Biochem Biophys Res Commun 2019;520:198-204.
80. Cohen JA, Bomben R, Pozzo F, et al. An updated perspective on current prognostic and predictive biomarkers in chronic lymphocytic leukemia in the context of chemoimmunotherapy and novel targeted therapy. Cancers (Basel) 2020;12:894.
81. Redondo-Muñoz J, Ugarte-Berzal E, Terol MJ, et al. Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain. Cancer Cell 2010;17:160-72.
82. Tissino E, Pozzo F, Benedetti D, et al. CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression. Blood 2020;135:1244-54.
83. Maffei R, Martinelli S, Castelli I, et al. Increased angiogenesis induced by chronic lymphocytic leukemia B cells is mediated by leukemia-derived Ang2 and VEGF. Leuk Res 2010;34:312-21.
84. Hacken E, Burger JA. Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia: Implications for disease pathogenesis and treatment. Biochim Biophys Acta 2016;1863:401-13.
85. Schulz A, Toedt G, Zenz T, Stilgenbauer S, Lichter P, Seiffert M. Inflammatory cytokines and signaling pathways are associated with survival of primary chronic lymphocytic leukemia cells in vitro: a dominant role of CCL2. Haematologica 2011;96:408-16.
86. Do HTT, Lee CH, Cho J. Chemokines and their receptors: multifaceted roles in cancer progression and potential value as cancer prognostic markers. Cancers (Basel) 2020;12:287.
87. Ugarte-Berzal E, Redondo-Muñoz J, Eroles P, et al. VEGF/VEGFR2 interaction down-regulates matrix metalloproteinase-9 via STAT1 activation and inhibits B chronic lymphocytic leukemia cell migration. Blood 2010;115:846-9.
88. Ma Z, Qin H, Benveniste EN. Transcriptional suppression of matrix metalloproteinase-9 gene expression by IFN-gamma and IFN-beta: critical role of STAT-1alpha. J Immunol 2001;167:5150-9.
89. Niu G, Wright KL, Huang M, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 2002;21:2000-8.
90. Chen Z, Han ZC. STAT3: a critical transcription activator in angiogenesis. Med Res Rev 2008;28:185-200.
91. Badoux X, Bueso-Ramos C, Harris D, et al. Cross-talk between chronic lymphocytic leukemia cells and bone marrow endothelial cells: role of signal transducer and activator of transcription 3. Hum Pathol 2011;42:1989-2000.
92. Gao P, Niu N, Wei T, et al. The roles of signal transducer and activator of transcription factor 3 in tumor angiogenesis. Oncotarget 2017;8:69139-61.
93. Lozano-Santos C, Martinez-Velasquez J, Fernandez-Cuevas B, et al. Vascular endothelial growth factor A (VEGFA) gene polymorphisms have an impact on survival in a subgroup of indolent patients with chronic lymphocytic leukemia. PLoS One 2014;9:e101063.
94. Góra-Tybor J, Szemraj J, Robak T, Jamroziak K. Clinical relevance of vascular endothelial growth factor type A (VEGFA) and VEGF receptor type 2 (VEGFR2) gene polymorphism in chronic lymphocytic leukemia. Blood Cells Mol Dis 2015;54:139-43.
95. Ballester S, Pineda B, Rodrigues P, Tormo E, Terol MJ, Eroles P. Clinical relevance of +936 C>T VEGFA and c.233C>T bFGF polymorphisms in chronic lymphocytic leukemia. Genes (Basel) 2020;11:686.
96. Martinelli S, Kanduri M, Maffei R, et al. ANGPT2 promoter methylation is strongly associated with gene expression and prognosis in chronic lymphocytic leukemia. Epigenetics 2013;8:720-9.
97. Kopparapu PK, Miranda C, Fogelstrand L, et al. MCPH1 maintains long-term epigenetic silencing of ANGPT2 in chronic lymphocytic leukemia. FEBS J 2015;282:1939-52.
98. Martinelli S, Maffei R, Fiorcari S, et al. The expression of endothelin-1 in chronic lymphocytic leukemia is controlled by epigenetic mechanisms and extracellular stimuli. Leuk Res 2017;54:17-24.
99. Trimarco V, Ave E, Facco M, et al. Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival. Oncotarget 2015;6:42130-49.
100. Mesaros O, Jimbu L, Neaga A, et al. Macrophage polarization in chronic lymphocytic leukemia: nurse-like cells are the caretakers of leukemic cells. Biomedicines 2020;8:516.
101. Fiorcari S, Maffei R, Atene CG, Potenza L, Luppi M, Marasca R. Nurse-like cells and chronic lymphocytic leukemia B cells: a mutualistic crosstalk inside tissue microenvironments. Cells 2021;10:217.
103. Riabov V, Gudima A, Wang N, Mickley A, Orekhov A, Kzhyshkowska J. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol 2014;5:75.
104. Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41:14-20.
105. Jaiswal S, Chao MP, Majeti R, Weissman IL. Macrophages as mediators of tumor immunosurveillance. Trends Immunol 2010;31:212-9.
106. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 2010;11:889-96.
107. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity 2014;41:49-61.
108. Audrito V, Serra S, Brusa D, et al. Extracellular nicotinamide phosphoribosyltransferase (NAMPT) promotes M2 macrophage polarization in chronic lymphocytic leukemia. Blood 2015;125:111-23.
109. Jia L, Clear A, Liu FT, et al. Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia. Blood 2014;123:1709-19.
110. Zajac E, Schweighofer B, Kupriyanova TA, et al. Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9. Blood 2013;122:4054-67.
111. Ardi VC, Kupriyanova TA, Deryugina EI, Quigley JP. Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis. Proc Natl Acad Sci U S A 2007;104:20262-7.
112. Deryugina EI, Zajac E, Juncker-Jensen A, Kupriyanova TA, Welter L, Quigley JP. Tissue-infiltrating neutrophils constitute the major in vivo source of angiogenesis-inducing MMP-9 in the tumor microenvironment. Neoplasia 2014;16:771-88.
113. Seignez C, Phillipson M. The multitasking neutrophils and their involvement in angiogenesis. Curr Opin Hematol 2017;24:3-8.
114. Christoffersson G, Vågesjö E, Vandooren J, et al. VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue. Blood 2012;120:4653-62.
115. Massena S, Christoffersson G, Vågesjö E, et al. Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans. Blood 2015;126:2016-26.
116. Manukyan G, Papajik T, Gajdos P, et al. Neutrophils in chronic lymphocytic leukemia are permanently activated and have functional defects. Oncotarget 2017;8:84889-901.
117. Podaza E, Risnik D, Colado A, et al. Chronic lymphocytic leukemia cells increase neutrophils survival and promote their differentiation into CD16high CD62Ldim immunosuppressive subset. Int J Cancer 2019;144:1128-34.
118. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 2013;200:373-83.
119. Liu Y, Shi K, Chen Y, et al. Exosomes and their role in cancer progression. Front Oncol 2021;11:639159.
120. Paggetti J, Haderk F, Seiffert M, et al. Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts. Blood 2015;126:1106-17.
121. Ghosh AK, Secreto CR, Knox TR, Ding W, Mukhopadhyay D, Kay NE. Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood 2010;115:1755-64.
122. Nisticò N, Maisano D, Iaccino E, et al. Role of chronic lymphocytic leukemia (cll)-derived exosomes in tumor progression and survival. Pharmaceuticals (Basel) 2020;13:244.
123. Yeh YY, Ozer HG, Lehman AM, et al. Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling. Blood 2015;125:3297-305.
124. Ferrajoli A, Shanafelt TD, Ivan C, et al. Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood 2013;122:1891-9.
125. Farahani M, Rubbi C, Liu L, Slupsky JR, Kalakonda N. CLL exosomes modulate the transcriptome and behaviour of recipient stromal cells and are selectively enriched in miR-202-3p. PLoS One 2015;10:e0141429.
126. Prieto D, Sotelo N, Seija N, et al. S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression. Blood 2017;130:777-88.
127. Geng HY, Feng ZJ, Zhang JJ, Li GY. Exosomal CLIC1 released by CLL promotes HUVECs angiogenesis by regulating ITGβ1-MAPK/ERK axis. Kaohsiung J Med Sci 2021;37:226-35.
128. Crompot E, Van Damme M, Pieters K, et al. Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications. Haematologica 2017;102:1594-604.
129. Till KJ, Spiller DG, Harris RJ, Chen H, Zuzel M, Cawley JC. CLL, but not normal, B cells are dependent on autocrine VEGF and alpha4beta1 integrin for chemokine-induced motility on and through endothelium. Blood 2005;105:4813-9.
130. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014;15:786-801.
131. García-pardo A, Opdenakker G. Nonproteolytic functions of matrix metalloproteinases in pathology and insights for the development of novel therapeutic inhibitors. Metalloproteinases Med 2015;2:19-28.
132. Bailón E, Aguilera-Montilla N, Gutiérrez-González A, et al. A catalytically inactive gelatinase B/MMP-9 mutant impairs homing of chronic lymphocytic leukemia cells by altering migration regulatory pathways. Biochem Biophys Res Commun 2018;495:124-30.
133. Vaisitti T, Serra S, Pepper C, et al. CD38 signals upregulate expression and functions of matrix metalloproteinase-9 in chronic lymphocytic leukemia cells. Leukemia 2013;27:1177-81.
134. Lee YK, Bone ND, Strege AK, Shanafelt TD, Jelinek DF, Kay NE. VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG), in B-cell chronic lymphocytic leukemia. Blood 2004;104:788-94.
135. Lee YK, Shanafelt TD, Bone ND, Strege AK, Jelinek DF, Kay NE. VEGF receptors on chronic lymphocytic leukemia (CLL) B cells interact with STAT 1 and 3: implication for apoptosis resistance. Leukemia 2005;19:513-23.
136. Pepper C, Ward R, Lin TT, et al. Highly purified CD38+ and CD38- sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin. Leukemia 2007;21:687-96.
137. Farahani M, Treweeke AT, Toh CH, et al. Autocrine VEGF mediates the antiapoptotic effect of CD154 on CLL cells. Leukemia 2005;19:524-30.
138. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 2008;8:604-17.
139. König A, Menzel T, Lynen S, et al. Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis. Leukemia 1997;11:258-65.
140. Bairey O, Zimra Y, Shaklai M, Rabizadeh E. Bcl-2 expression correlates positively with serum basic fibroblast growth factor (bFGF) and negatively with cellular vascular endothelial growth factor (VEGF) in patients with chronic lymphocytic leukaemia. Br J Haematol 2001;113:400-6.
141. Romanov VV, James CH, Sherrington PD, Pettitt AR. Basic fibroblast growth factor suppresses p53 activation in the neoplastic cells of a proportion of patients with chronic lymphocytic leukaemia. Oncogene 2005;24:6855-60.
142. Martinez-Torres AC, Quiney C, Attout T, et al. CD47 agonist peptides induce programmed cell death in refractory chronic lymphocytic leukemia B cells via PLCγ1 activation: evidence from mice and humans. PLoS Med 2015;12:e1001796.
143. Ringshausen I, Dechow T, Schneller F, et al. Constitutive activation of the MAPkinase p38 is critical for MMP-9 production and survival of B-CLL cells on bone marrow stromal cells. Leukemia 2004;18:1964-70.
145. Kohlhaas V, Blakemore SJ, Al-Maarri M, et al. Active Akt signaling triggers CLL toward Richter transformation via overactivation of Notch1. Blood 2021;137:646-60.
146. Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005;23:4079-88.
147. Molica S, Vacca A, Tucc L, Ribatti D. Reversal of bone marrow angiogenesis in chronic lymphocytic leukemia following fludarabine therapy. Haematologica 2005;90:698-700.
148. Molica S, Montillo M, Ribatti D, et al. Intense reversal of bone marrow angiogenesis after sequential fludarabine-induction and alemtuzumab-consolidation therapy in advanced chronic lymphocytic leukemia. Haematologica 2007;92:1367-74.
149. López-Guerra M, Xargay-Torrent S, Rosich L, et al. The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells. Leukemia 2015;29:96-106.
150. Maffei R, Fiorcari S, Vaisitti T, et al. Macitentan, a double antagonist of endothelin receptors, efficiently impairs migration and microenvironmental survival signals in chronic lymphocytic leukemia. Oncotarget 2017;8:90013-27.
151. Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993;177:1675-80.
152. D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 1994;91:4082-5.
153. Chanan-Khan A, Miller KC, Takeshita K, et al. Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL). Blood 2005;106:3348-52.
154. Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36.
155. Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol 2006;24:5343-9.
156. Ferrajoli A, Lee BN, Schlette EJ, et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 2008;111:5291-7.
157. Maffei R, Fiorcari S, Bulgarelli J, et al. Endothelium-mediated survival of leukemic cells and angiogenesis-related factors are affected by lenalidomide treatment in chronic lymphocytic leukemia. Exp Hematol 2014;42:126-36.e1.
158. Aue G, Nelson Lozier J, Tian X, et al. Inflammation, TNFα and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia. Am J Hematol 2011;86:835-40.
159. Egle A, Steurer M, Melchardt T, et al. Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study. Ann Hematol 2018;97:1825-39.
160. Mauro FR, Carella AM, Molica S, et al. Fludarabine, cyclophosphamide and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia. A multicenter phase I-II GIMEMA trial. Leuk Lymphoma 2017;58:1640-7.
161. Strati P, Takahashi K, Peterson CB, et al. Efficacy and predictors of response of lenalidomide and rituximab in patients with treatment-naive and relapsed CLL. Blood Adv 2019;3:1533-9.
162. Ossenkoppele GJ, Stussi G, Maertens J, et al. Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK). Blood 2012;120:4706-11.
163. Paesler J, Gehrke I, Poll-Wolbeck SJ, Kreuzer KA. Targeting the vascular endothelial growth factor in hematologic malignancies. Eur J Haematol 2012;89:373-84.
164. Bogusz J, Majchrzak A, Mędra A, Cebula-Obrzut B, Robak T, Smolewski P. Mechanisms of action of the anti-VEGF monoclonal antibody bevacizumab on chronic lymphocytic leukemia cells. Postepy Hig Med Dosw (Online) 2013;67:107-18.
165. Shanafelt T, Zent C, Byrd J, et al. Phase II trials of single-agent anti-VEGF therapy for patients with chronic lymphocytic leukemia. Leuk Lymphoma 2010;51:2222-9.
166. Kay NE, Strati P, LaPlant BR, et al. A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia. Oncotarget 2016;7:78269-80.
167. Paesler J, Gehrke I, Gandhirajan RK, et al. The vascular endothelial growth factor receptor tyrosine kinase inhibitors vatalanib and pazopanib potently induce apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Clin Cancer Res 2010;16:3390-8.
168. Cornwall S, Cull G, Joske D, Ghassemifar R. Green tea polyphenol "epigallocatechin-3-gallate", differentially induces apoptosis in CLL B-and T-Cells but not in healthy B-and T-Cells in a dose dependant manner. Leuk Res 2016;51:56-61.
169. Huber S, Oelsner M, Decker T, et al. Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1. Leukemia 2011;25:838-47.
170. Messmer D, Fecteau JF, O'Hayre M, Bharati IS, Handel TM, Kipps TJ. Chronic lymphocytic leukemia cells receive RAF-dependent survival signals in response to CXCL12 that are sensitive to inhibition by sorafenib. Blood 2011;117:882-9.