The pathogenic relevance of the prognostic markers CD38 and CD49d in chronic lymphocytic leukemia

Annals of Hematology

Volumn 93, Issue 3, 2014, Pages 361-374

  Brachtl, Gabriele ^a   Piñón Hofbauer, Josefina ^a   Greil, Richard ^a   Hartmann, Tanja Nicole ^a  

^a PARACELSUS MEDICAL UNIVERSITY   (Austria)

Author keywords

CD38; CD49d; Chronic lymphocytic leukemia; Microenvironment; VLA 4

Indexed keywords

ANIMALS; ANTIGENS, CD38; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; HUMANS; INTEGRIN ALPHA4; INTEGRIN ALPHA4BETA1; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MEMBRANE GLYCOPROTEINS; MODELS, BIOLOGICAL; NEOPLASM PROTEINS; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL; TUMOR MICROENVIRONMENT;

EID: 84894358095     PISSN: 09395555     EISSN: 14320584     Source Type: Journal    
DOI: 10.1007/s00277-013-1967-y     Document Type: Review

References (131)

1. Chiorazzi N, Rai KR, Ferrarini M (2005) Chronic lymphocytic leukemia. N Engl J Med 352(8):804-815. doi: 10.1056/NEJMra041720
2. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS (1975) Clinical staging of chronic lymphocytic leukemia. Blood 46(2):219-234
3. Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, Vaugier G, Potron G, Colona P, Oberling F, Thomas M, Tchernia G, Jacquillat C, Boivin P, Lesty C, Duault MT, Monconduit M, Belabbes S, Gremy F (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48(1):198-206
4. Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343(26):1910-1916. doi: 10.1056/ NEJM200012283432602
5. Dal-Bo M, Bertoni F, Forconi F, Zucchetto A, Bomben R, Marasca R, Deaglio S, Laurenti L, Efremov DG, Gaidano G, Del Poeta G, Gattei V (2009) Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance. J Transl Med 7:76. doi: 10.1186/1479-5876-7-76
6. Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, Buchbinder A, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Vinciguerra VP, Rai KR, Ferrarini M, Chiorazzi N (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94(6):1840-1847
7. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK (1999) Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94(6):1848-1854
8. Chen L, Widhopf G, Huynh L, Rassenti L, Rai KR, Weiss A, Kipps TJ (2002) Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood 100(13):4609-4614. doi: 10.1182/blood-2002- 06-1683
9. Wiestner A, Rosenwald A, Barry TS, Wright G, Davis RE, Henrickson SE, Zhao H, Ibbotson RE, Orchard JA, Davis Z, Stetler-Stevenson M, Raffeld M, Arthur DC, Marti GE, Wilson WH, Hamblin TJ, Oscier DG, Staudt LM (2003) ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood 101(12):4944-4951. doi: 10.1182/blood-2002-10-3306
10. Gattei V, Bulian P, Del Principe MI, Zucchetto A, Maurillo L, Buccisano F, Bomben R, Dal-Bo M, Luciano F, Rossi FM, Degan M, Amadori S, Del Poeta G (2008) Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia. Blood 111(2):865-873. doi: 10.1182/blood-2007-05-092486
11. Shanafelt TD, Geyer SM, Bone ND, Tschumper RC, Witzig TE, Nowakowski GS, Zent CS, Call TG, Laplant B, Dewald GW, Jelinek DF, Kay NE (2008) CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. Br J Haematol 140(5):537-546. doi: 10.1111/j.1365-2141.2007.06965.x
12. Messmer BT, Messmer D, Allen SL, Kolitz JE, Kudalkar P, Cesar D, Murphy EJ, Koduru P, Ferrarini M, Zupo S, Cutrona G, Damle RN, Wasil T, Rai KR, Hellerstein MK, Chiorazzi N (2005) In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest 115(3):755-764. doi: 10.1172/JCI23409
13. Carbone A, Gloghini A, Gruss HJ, Pinto A (1995) CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease. Am J Pathol 147(4):912-922
14. Ghia P, Strola G, Granziero L, Geuna M, Guida G, Sallusto F, Ruffing N, Montagna L, Piccoli P, Chilosi M, Caligaris-Cappio F (2002) Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L + T cells by producing CCL22. Eur J Immunol 32(5):1403-1413. doi: 10.1002/1521- 4141(200205)32:5<1403::AID-IMMU1403>3.0.CO;2-Y
15. Patten PE, Buggins AG, Richards J, Wotherspoon A, Salisbury J, Mufti GJ, Hamblin TJ, Devereux S (2008) CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment. Blood 111(10):5173-5181. doi: 10.1182/blood-2007-08-108605
16. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ (2000) Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood 96(8):2655-2663
17. Kay NE, Shanafelt TD, Strege AK, Lee YK, Bone ND, Raza A (2007) 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 31(7):899-906. doi: 10.1016/j.leukres.2006.11.024
18. Panayiotidis P, Jones D, Ganeshaguru K, Foroni L, Hoffbrand AV (1996) Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. Br J Haematol 92(1):97-103
19. Kurtova AV, Balakrishnan K, Chen R, Ding W, Schnabl S, Quiroga MP, Sivina M, Wierda WG, Estrov Z, Keating MJ, Shehata M, Jager U, Gandhi V, Kay NE, Plunkett W, Burger JA (2009) Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance. Blood 114(20):4441-4450. doi: 10.1182/blood-2009-07-233718
20. Ramsay AG, Johnson AJ, Lee AM, Gorgun G, Le Dieu R, Blum W, Byrd JC, Gribben JG (2008) Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest 118(7):2427-2437. doi: 10.1172/JCI35017
21. Cols M, Barra CM, He B, Puga I, Xu W, Chiu A, Tam W, Knowles DM, Dillon SR, Leonard JP, Furman RR, Chen K, Cerutti A (2012) Stromal endothelial cells establish a bidirectional crosstalk with chronic lymphocytic leukemia cells through the TNF-related factors BAFF, APRIL, and CD40L. J Immunol 188(12):6071-6083. doi: 10.4049/jimmunol.1102066
22. Ding W, Knox TR, Tschumper RC, Wu W, Schwager SM, Boysen JC, Jelinek DF, Kay NE (2010) 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 116(16):2984-2993. doi: 10.1182/blood-2010-02-269894
23. Ding W, Nowakowski GS, Knox TR, Boysen JC, Maas ML, Schwager SM, Wu W, Wellik LE, Dietz AB, Ghosh AK, Secreto CR, Medina KL, Shanafelt TD, Zent CS, Call TG, Kay NE (2009) Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression. Br J Haematol 147(4):471-483. doi: 10.1111/j.1365-2141.2009.07868.x
24. Lutzny G, Kocher T, Schmidt-Supprian M, Rudelius M, Klein-Hitpass L, Finch AJ, Durig J, Wagner M, Haferlach C, Kohlmann A, Schnittger S, Seifert M, Wanninger S, Zaborsky N, Oostendorp R, Ruland J, Leitges M, Kuhnt T, Schafer Y, Lampl B, Peschel C, Egle A, Ringshausen I (2013) Protein kinase c-beta-dependent activation of NF-kappaB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo. Cancer Cell 23(1):77-92. doi: 10.1016/j.ccr.2012.12.003
25. Bottcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, Fink AM, Buhler A, Zenz T, Wenger MK, Mendila M, Wendtner CM, Eichhorst BF, Dohner H, Hallek MJ, Kneba M (2012) Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol Off J Am Soc Clin Oncol 30(9):980-988. doi: 10.1200/JCO.2011.36.9348
26. Kwok M, Rawstron A, Varghese A, Hillmen P (2009) Minimal residual disease is a predictor for progression-free and overall survival in chronic lymphocytic leukemia (CLL) that is independent of the type or line of therapy. Blood 114 (22):Abstract 540
27. Moreton P, Kennedy B, Lucas G, Leach M, Rassam SM, Haynes A, Tighe J, Oscier D, Fegan C, Rawstron A, Hillmen P (2005) Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol Off J Am Soc Clin Oncol 23(13):2971-2979. doi: 10.1200/JCO.2005.04.021
28. Alessio M, Roggero S, Funaro A, De Monte LB, Peruzzi L, Geuna M, Malavasi F (1990) CD38 molecule: structural and biochemical analysis on human T lymphocytes, thymocytes, and plasma cells. J Immunol 145(3):878-884
29. Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q (2005) Crystal structure of human CD38 extracellular domain. Structure 13(9):1331-1339. doi: 10.1016/j.str.2005.05.012
30. Adebanjo OA, Anandatheerthavarada HK, Koval AP, Moonga BS, Biswas G, Sun L, Sodam BR, Bevis PJ, Huang CL, Epstein S, Lai FA, Avadhani NG, Zaidi M (1999) A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis. Nat Cell Biol 1(7):409-414. doi: 10.1038/15640
31. Malavasi F, Deaglio S, Funaro A, Ferrero E, Horenstein AL, Ortolan E, Vaisitti T, Aydin S (2008) Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev 88(3):841-886. doi: 10.1152/physrev.00035.2007
32. Guse AH (1999) Cyclic ADP-ribose: a novel Ca2 +-mobilising second messenger. Cell Signal 11(5):309-316
33. Gustafsson AJ, Muraro L, Dahlberg C, Migaud M, Chevallier O, Khanh HN, Krishnan K, Li N, Islam MS (2011) ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor. Mol Cell Endocrinol 333(1):8-19. doi: 10.1016/j.mce.2010.11.004
34. Magnone M, Bauer I, Poggi A, Mannino E, Sturla L, Brini M, Zocchi E, De Flora A, Nencioni A, Bruzzone S (2012) NAD + levels control Ca2+ stores replenishment and mitogen-induced increase of cytosolic Ca2+ by ADPR-dependent TRPM2 gating in human T lymphocytes. J Biol Chem. doi: 10.1074/jbc.M111.324269
35. Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP, Scharenberg AM (2001) ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411(6837):595-599. doi: 10.1038/35079100
36. Sano Y, Inamura K, Miyake A, Mochizuki S, Yokoi H, Matsushime H, Furuichi K (2001) Immunocyte Ca2+ influx system mediated by LTRPC2. Science 293(5533):1327-1330. doi: 10.1126/science.1062473
37. Sumoza-Toledo A, Penner R (2011) TRPM2: a multifunctional ion channel for calcium signalling. J Physiol 589(Pt 7):1515-1525. doi: 10.1113/jphysiol.2010. 201855
38. Partida-Sanchez S, Cockayne DA, Monard S, Jacobson EL, Oppenheimer N, Garvy B, Kusser K, Goodrich S, Howard M, Harmsen A, Randall TD, Lund FE (2001) Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med 7(11):1209-1216. doi: 10.1038/nm1101-1209
39. Partida-Sanchez S, Goodrich S, Kusser K, Oppenheimer N, Randall TD, Lund FE (2004) Regulation of dendritic cell trafficking by the ADP-ribosyl cyclase CD38: impact on the development of humoral immunity. Immun 20(3):279-291
40. Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y (2008) TRPM2-mediated Ca2 + influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14(7):738-747. doi: 10.1038/nm1758
41. Johnson JD, Ford EL, Bernal-Mizrachi E, Kusser KL, Luciani DS, Han Z, Tran H, Randall TD, Lund FE, Polonsky KS (2006) Suppressed insulin signaling and increased apoptosis in CD38-null islets. Diabetes 55(10):2737-2746. doi: 10.2337/db05-1455
42. Kato I, Yamamoto Y, Fujimura M, Noguchi N, Takasawa S, Okamoto H (1999) CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion. J Biol Chem 274(4):1869-1872
43. Higashida H, Yokoyama S, Munesue T, Kikuchi M, Minabe Y, Lopatina O (2011) CD38 gene knockout juvenile mice: a model of oxytocin signal defects in autism. Biol Pharm Bull 34(9):1369-1372
44. Jin D, Liu HX, Hirai H, Torashima T, Nagai T, Lopatina O, Shnayder NA, Yamada K, Noda M, Seike T, Fujita K, Takasawa S, Yokoyama S, Koizumi K, Shiraishi Y, Tanaka S, Hashii M, Yoshihara T, Higashida K, Islam MS, Yamada N, Hayashi K, Noguchi N, Kato I, Okamoto H, Matsushima A, Salmina A, Munesue T, Shimizu N, Mochida S, Asano M, Higashida H (2007) CD38 is critical for social behaviour by regulating oxytocin secretion. Nature 446(7131):41-45. doi: 10.1038/nature05526
45. Salmina AB, Lopatina O, Ekimova MV, Mikhutkina SV, Higashida H (2010) CD38/cyclic ADP-ribose system: a new player for oxytocin secretion and regulation of social behaviour. J Neuroendocrinol 22(5):380-392. doi: 10.1111/j.1365-2826.2010.01970.x
46. Sun L, Iqbal J, Dolgilevich S, Yuen T, Wu XB, Moonga BS, Adebanjo OA, Bevis PJ, Lund F, Huang CL, Blair HC, Abe E, Zaidi M (2003) Disordered osteoclast formation and function in a CD38 (ADP-ribosyl cyclase)-deficient mouse establishes an essential role for CD38 in bone resorption. FASEB J: Off Publ Fed Am Soc Exp Biol 17(3):369-375. doi: 10.1096/fj.02-0205com
47. Deshpande DA, White TA, Guedes AG, Milla C, Walseth TF, Lund FE, Kannan MS (2005) Altered airway responsiveness in CD38-deficient mice. Am J Respir Cell Mol Biol 32(2):149-156. doi: 10.1165/rcmb.2004-0243OC
48. Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, Dianzani U, Stockinger H, Malavasi F (1998) Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member. J Immunol 160(1):395-402
49. Dianzani U, Funaro A, DiFranco D, Garbarino G, Bragardo M, Redoglia V, Buonfiglio D, De Monte LB, Pileri A, Malavasi F (1994) Interaction between endothelium and CD4 + CD45RA + lymphocytes. Role of the human CD38 molecule. J Immunol 153(3):952-959
50. Kumagai M, Coustan-Smith E, Murray DJ, Silvennoinen O, Murti KG, Evans WE, Malavasi F, Campana D (1995) Ligation of CD38 suppresses human B lymphopoiesis. J Exp Med 181(3):1101-1110
51. Zupo S, Rugari E, Dono M, Taborelli G, Malavasi F, Ferrarini M (1994) CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells. Eur J Immunol 24(5):1218-1222. doi: 10.1002/eji.1830240532
52. Funaro A, Morra M, Calosso L, Zini MG, Ausiello CM, Malavasi F (1997) Role of the human CD38 molecule in B cell activation and proliferation. Tissue Antigens 49(1):7-15
53. Hemler ME, Elices MJ, Parker C, Takada Y (1990) Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions. Immunol Rev 114:45-65
54. Berlin C, Berg EL, Briskin MJ, Andrew DP, Kilshaw PJ, Holzmann B, Weissman IL, Hamann A, Butcher EC (1993) Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74(1):185-195
55. Berlin C, Bargatze RF, Campbell JJ, von Andrian UH, Szabo MC, Hasslen SR, Nelson RD, Berg EL, Erlandsen SL, Butcher EC (1995) Alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80(3):413-422
56. Rose DM, Han J, Ginsberg MH (2002) Alpha4 integrins and the immune response. Immunol Rev 186:118-124
57. Hartmann TN, Grabovsky V, Wang W, Desch P, Rubenzer G, Wollner S, Binsky I, Vallon-Eberhard A, Sapoznikov A, Burger M, Shachar I, Haran M, Honczarenko M, Greil R, Alon R (2009) Circulating B-cell chronic lymphocytic leukemia cells display impaired migration to lymph nodes and bone marrow. Cancer Res 69(7):3121-3130. doi: 10.1158/0008-5472.CAN-08-4136
58. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60(4):577-584
59. Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R (1989) Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59(6):1203-1211
60. Guan JL, Hynes RO (1990) Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Cell 60(1):53-61
61. Rettig MP, Ansstas G, DiPersio JF (2012) Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4. Leuk Off J Leuk Soc Am Leuk Res Fund UK 26(1):34-53. doi: 10.1038/leu.2011.197
62. Hirsch E, Iglesias A, Potocnik AJ, Hartmann U, Fassler R (1996) Impaired migration but not differentiation of haematopoietic stem cells in the absence of beta1 integrins. Nature 380(6570):171-175. doi: 10.1038/380171a0
63. Fassler R, Meyer M (1995) Consequences of lack of beta 1 integrin gene expression in mice. Genes Dev 9(15):1896-1908
64. Bungartz G, Stiller S, Bauer M, Muller W, Schippers A, Wagner N, Fassler R, Brakebusch C (2006) Adult murine hematopoiesis can proceed without beta1 and beta7 integrins. Blood 108(6):1857-1864. doi: 10.1182/blood-2005-10-007658
65. Arroyo AG, Yang JT, Rayburn H, Hynes RO (1996) Differential requirements for alpha4 integrins during fetal and adult hematopoiesis. Cell 85(7):997-1008
66. Arroyo AG, Yang JT, Rayburn H, Hynes RO (1999) Alpha4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo. Immunity 11(5):555-566
67. Scott LM, Priestley GV, Papayannopoulou T (2003) Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing. Mol Cell Biol 23(24):9349-9360
68. Priestley GV, Ulyanova T, Papayannopoulou T (2007) Sustained alterations in biodistribution of stem/progenitor cells in Tie2Cre + alpha4(f/f) mice are hematopoietic cell autonomous. Blood 109(1):109-111. doi: 10.1182/blood-2006-06- 026427
69. Priestley GV, Scott LM, Ulyanova T, Papayannopoulou T (2006) Lack of alpha4 integrin expression in stem cells restricts competitive function and self-renewal activity. Blood 107(7):2959-2967. doi: 10.1182/blood-2005-07-2670
70. Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106(6):1901-1910. doi: 10.1182/blood-2005-04-1417
71. Kollet O, Spiegel A, Peled A, Petit I, Byk T, Hershkoviz R, Guetta E, Barkai G, Nagler A, Lapidot T (2001) Rapid and efficient homing of human CD34(+)CD38(-/low)CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood 97(10):3283-3291
72. Peled A, Kollet O, Ponomaryov T, Petit I, Franitza S, Grabovsky V, Slav MM, Nagler A, Lider O, Alon R, Zipori D, Lapidot T (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 95(11):3289-3296
73. Chigaev A, Sklar LA (2012) Aspects of VLA-4 and LFA-1 regulation that may contribute to rolling and firm adhesion. Front Immunol 3:242. doi: 10.3389/fimmu.2012.00242
74. Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, Akiyama T, Kuroda H, Kawano Y, Kobune M, Kato J, Hirayama Y, Sakamaki S, Kohda K, Miyake K, Niitsu Y (2003) Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med 9(9):1158-1165. doi: 10.1038/nm909
75. Oostendorp RA, Dormer P (1997) VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells. Leuk Lymphoma 24(5-6):423-435
76. Hamblin TJ, Orchard JA, Ibbotson RE, Davis Z, Thomas PW, Stevenson FK, Oscier DG (2002) CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood 99(3):1023-1029
77. Del Poeta G, Maurillo L, Venditti A, Buccisano F, Epiceno AM, Capelli G, Tamburini A, Suppo G, Battaglia A, Del Principe MI, Del Moro B, Masi M, Amadori S (2001) Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 98(9):2633-2639
78. Durig J, Naschar M, Schmucker U, Renzing-Kohler K, Holter T, Huttmann A, Duhrsen U (2002) CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leuk Off J Leuk Soc Am Leuk Res Fund UK 16(1):30-35. doi: 10.1038/sj.leu.2402339
79. Ibrahim S, Keating M, Do KA, O'Brien S, Huh YO, Jilani I, Lerner S, Kantarjian HM, Albitar M (2001) CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood 98(1):181-186
80. Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P, Dohner H, Stilgenbauer S (2002) V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 100(4):1410-1416
81. Thornton PD, Fernandez C, Giustolisi GM, Morilla R, Atkinson S, A'Hern RP, Matutes E, Catovsky D (2004) CD38 expression as a prognostic indicator in chronic lymphocytic leukaemia. Hematol J: Off J Eur Haematol Assoc / EHA 5(2):145-151. doi: 10.1038/sj.thj.6200360
82. Vroblova V, Smolej L, Vrbacky F, Jankovicova K, Hrudkova M, Maly J, Krejsek J (2009) Biological prognostic markers in chronic lymphocytic leukemia. Acta Med (Hradec Kralove) 52(1):3-8
83. Montserrat E (2006) New prognostic markers in CLL. Hematology/the Education Program of the American Society of Hematology American Society of Hematology Education Program:279-284. doi: 10.1182/asheducation-2006.1.279
84. Nuckel H, Switala M, Collins CH, Sellmann L, Grosse-Wilde H, Duhrsen U, Rebmann V (2009) High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia. Clin Immunol 131(3):472-480. doi: 10.1016/j.clim.2009.02.004
85. Majid A, Lin TT, Best G, Fishlock K, Hewamana S, Pratt G, Yallop D, Buggins AG, Wagner S, Kennedy BJ, Miall F, Hills R, Devereux S, Oscier DG, Dyer MJ, Fegan C, Pepper C (2011) CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL. Leuk Res 35(6):750-756. doi: 10.1016/j.leukres.2010.10.022
86. Brachtl G, Sahakyan K, Denk U, Girbl T, Alinger B, Hofbauer SW, Neureiter D, Hofbauer JP, Egle A, Greil R, Hartmann TN (2011) Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. PloS One 6(8):e23758. doi: 10.1371/journal.pone.0023758
87. Rossi D, Bodoni CL, Zucchetto A, Rasi S, De Paoli L, Fangazio M, Rossi FM, Ladetto M, Gattei V, Gaidano G (2010) Low CD49d expression and long telomere identify a chronic lymphocytic leukemia subset with highly favourable outcome. Am J Hematol 85(8):619-622. doi: 10.1002/ajh.21756
88. Rossi D, Zucchetto A, Rossi FM, Capello D, Cerri M, Deambrogi C, Cresta S, Rasi S, De Paoli L, Bodoni CL, Bulian P, Del Poeta G, Ladetto M, Gattei V, Gaidano G (2008) CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia. Haematologica 93(10):1575-1579. doi: 10.3324/haematol.13103
89. Eksioglu-Demiralp E, Alpdogan O, Aktan M, Firatli T, Ozturk A, Budak T, Bayik M, Akoglu T (1996) Variable expression of CD49d antigen in B cell chronic lymphocytic leukemia is related to disease stages. Leuk Off J Leuk Soc Am Leuk Res Fund UK 10(8):1331-1339
90. Zucchetto A, Bomben R, Dal Bo M, Bulian P, Benedetti D, Nanni P, Del Poeta G, Degan M, Gattei V (2006) CD49d in B-cell chronic lymphocytic leukemia: correlated expression with CD38 and prognostic relevance. Leuk Off J Leuk Soc Am Leuk Res Fund UK 20(3):523-525. doi: 10.1038/sj.leu.2404087, author reply 528-529
91. Zucchetto A, Bomben R, Dal Bo M, Sonego P, Nanni P, Rupolo M, Bulian P, Dal Maso L, Del Poeta G, Del Principe MI, Degan M, Gattei V (2006) A scoring system based on the expression of six surface molecules allows the identification of three prognostic risk groups in B-cell chronic lymphocytic leukemia. J Cell Physiol 207(2):354-363. doi: 10.1002/jcp.20570
92. Chen JR, Gu BJ, Dao LP, Bradley CJ, Mulligan SP, Wiley JS (1999) Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down-regulation of both L-selectin and CD23. Br J Haematol 105(1):181-189
93. Bazerbashi MB, Reeve J, Chanarin I (1978) Studies in chronic lymphocytic leukaemia. The kinetics of 51Cr-labelled lymphocytes. Scand J Haematol 20(1):37-51
94. Gu B, Dao LP, Wiley J (2001) Impaired transendothelial migration of B-CLL lymphocytes: a defect linked to low L-selectin expression. Leuk Lymphoma 42(1-2):5-12. doi: 10.3109/10428190109097671
95. Till KJ, Lin K, Zuzel M, Cawley JC (2002) The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Blood 99(8):2977-2984
96. Till KJ, Spiller DG, Harris RJ, Chen H, Zuzel M, Cawley JC (2005) CLL, but not normal, B cells are dependent on autocrine VEGF and alpha4beta1 integrin for chemokine-induced motility on and through endothelium. Blood 105(12):4813-4819. doi: 10.1182/blood-2004-10-4054
97. Deaglio S, Vaisitti T, Aydin S, Bergui L, D'Arena G, Bonello L, Omede P, Scatolini M, Jaksic O, Chiorino G, Efremov D, Malavasi F (2007) CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood 110(12):4012-4021. doi: 10.1182/blood-2007-06-094029
98. Vaisitti T, Aydin S, Rossi D, Cottino F, Bergui L, D'Arena G, Bonello L, Horenstein AL, Brennan P, Pepper C, Gaidano G, Malavasi F, Deaglio S (2010) CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells. Leuk Off J Leuk Soc Am Leuk Res Fund UK 24(5):958-969. doi: 10.1038/leu.2010.36
99. Pittner BT, Shanafelt TD, Kay NE, Jelinek DF (2005) CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulation. Leuk Off J Leuk Soc Am Leuk Res Fund UK 19(12):2264-2272. doi: 10.1038/sj.leu.2403975
100. Aydin S, Grabellus F, Eisele L, Mollmann M, Hanoun M, Ebeling P, Moritz T, Carpinteiro A, Nuckel H, Sak A, Gothert JR, Duhrsen U, Durig J (2011) Investigating the role of CD38 and functionally related molecular risk factors in the CLL NOD/SCID xenograft model. Eur J Haematol 87(1):10-19. doi: 10.1111/j.1600-0609.2011.01626.x
101. Deaglio S, Capobianco A, Bergui L, Durig J, Morabito F, Duhrsen U, Malavasi F (2003) CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells. Blood 102(6):2146-2155. doi: 10.1182/blood-2003-03-0989
102. Deaglio S, Vaisitti T, Bergui L, Bonello L, Horenstein AL, Tamagnone L, Boumsell L, Malavasi F (2005) CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Blood 105(8):3042-3050. doi: 10.1182/blood-2004-10-3873
103. Hamilton E, Pearce L, Morgan L, Robinson S, Ware V, Brennan P, Thomas NS, Yallop D, Devereux S, Fegan C, Buggins AG, Pepper C (2012) Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells. Br J Haematol 158(5):589-599. doi: 10.1111/j.1365-2141.2012.09191.x
104. Tonino SH, Spijker R, Luijks DM, van Oers MH, Kater AP (2008) No convincing evidence for a role of CD31-CD38 interactions in the pathogenesis of chronic lymphocytic leukemia. Blood 112(3):840-843. doi: 10.1182/blood-2008-03- 144576
105. Deaglio S, Aydin S, Grand MM, Vaisitti T, Bergui L, D'Arena G, Chiorino G, Malavasi F (2010) CD38/CD31 interactions activate genetic pathways leading to proliferation and migration in chronic lymphocytic leukemia cells. Mol Med 16(3-4):87-91. doi: 10.2119/molmed.2009.00146
106. Lagneaux L, Delforge A, De Bruyn C, Bernier M, Bron D (1999) Adhesion to bone marrow stroma inhibits apoptosis of chronic lymphocytic leukemia cells. Leuk Lymphoma 35(5-6):445-453. doi: 10.1080/10428199909169609
107. de la Fuente MT, Casanova B, Garcia-Gila M, Silva A, Garcia-Pardo A (1999) Fibronectin interaction with alpha4beta1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia: correlation with Bcl-2 and Bax. Leuk Off J Leuk Soc Am Leuk Res Fund UK 13(2):266-274
108. de la Fuente MT, Casanova B, Moyano JV, Garcia-Gila M, Sanz L, Garcia-Marco J, Silva A, Garcia-Pardo A (2002) Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine. J Leukoc Biol 71(3):495-502
109. Pedersen IM, Kitada S, Leoni LM, Zapata JM, Karras JG, Tsukada N, Kipps TJ, Choi YS, Bennett F, Reed JC (2002) Protection of CLL B cells by a follicular dendritic cell line is dependent on induction of Mcl-1. Blood 100(5):1795-1801
110. Zucchetto A, Vaisitti T, Benedetti D, Tissino E, Bertagnolo V, Rossi D, Bomben R, Dal Bo M, Del Principe MI, Gorgone A, Pozzato G, Gaidano G, Del Poeta G, Malavasi F, Deaglio S, Gattei V (2012) The CD49d/CD29 complex is physically and functionally associated with CD38 in B-cell chronic lymphocytic leukemia cells. Leuk Off J Leuk Soc Am Leuk Res Fund UK 26(6):1301-1312. doi: 10.1038/leu.2011.369
111. Coscia M, Pantaleoni F, Riganti C, Vitale C, Rigoni M, Peola S, Castella B, Foglietta M, Griggio V, Drandi D, Ladetto M, Bosia A, Boccadoro M, Massaia M (2011) IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells. Leuk Off J Leuk Soc Am Leuk Res Fund UK 25(5):828-837. doi: 10.1038/leu.2011.12
112. Binsky I, Lantner F, Grabovsky V, Harpaz N, Shvidel L, Berrebi A, Goldenberg DM, Leng L, Bucala R, Alon R, Haran M, Shachar I (2010) TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. J Immunol 184(9):4761-4769. doi: 10.4049/jimmunol.0904149
113. Buggins AG, Pepper C, Patten PE, Hewamana S, Gohil S, Moorhead J, Folarin N, Yallop D, Thomas NS, Mufti GJ, Fegan C, Devereux S (2010) Interaction with vascular endothelium enhances survival in primary chronic lymphocytic leukemia cells via NF-kappaB activation and de novo gene transcription. Cancer Res 70(19):7523-7533. doi: 10.1158/0008-5472.CAN-10-1634
114. Redondo-Munoz J, Escobar-Diaz E, Samaniego R, Terol MJ, Garcia-Marco JA, Garcia-Pardo A (2006) 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 108(9):3143-3151. doi: 10.1182/blood-2006-03-007294
115. Redondo-Munoz J, Ugarte-Berzal E, Terol MJ, Van den Steen PE, Hernandez del Cerro M, Roderfeld M, Roeb E, Opdenakker G, Garcia-Marco JA, Garcia-Pardo A (2010) Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain. Cancer Cell 17(2):160-172. doi: 10.1016/j.ccr.2009.12.044
116. Calissano C, Damle RN, Hayes G, Murphy EJ, Hellerstein MK, Moreno C, Sison C, Kaufman MS, Kolitz JE, Allen SL, Rai KR, Chiorazzi N (2009) In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia. Blood 114(23):4832-4842. doi: 10.1182/blood-2009-05-219634
117. Damle RN, Calissano C, Chiorazzi N (2010) Chronic lymphocytic leukaemia: a disease of activated monoclonal B cells. Best Pract Res Clin Haematol 23(1):33-45. doi: 10.1016/j.beha.2010.02.001
118. Damle RN, Temburni S, Calissano C, Yancopoulos S, Banapour T, Sison C, Allen SL, Rai KR, Chiorazzi N (2007) CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells. Blood 110(9):3352-3359. doi: 10.1182/blood-2007-04-083832
119. Lin TT, Hewamana S, Ward R, Taylor H, Payne T, Pratt G, Baird D, Fegan C, Pepper C (2008) Highly purified CD38 sub-populations show no evidence of preferential clonal evolution despite having increased proliferative activity when compared with CD38 sub-populations derived from the same chronic lymphocytic leukaemia patient. Br J Haematol 142(4):595-605. doi: 10.1111/j.1365-2141.2008.07236.x
120. Bennett F, Rawstron A, Plummer M, de Tute R, Moreton P, Jack A, Hillmen P (2007) B-cell chronic lymphocytic leukaemia cells show specific changes in membrane protein expression during different stages of cell cycle. Br J Haematol 139(4):600-604. doi: 10.1111/j.1365-2141.2007.06790.x
121. Asslaber D, Grossinger EM, Girbl T, Hofbauer SW, Egle A, Weiss L, Greil R, Hartmann TN (2013) Mimicking the microenvironment in chronic lymphocytic leukaemia - where does the journey go? Br J Haematol 160(5):711-714. doi: 10.1111/bjh.12151
122. Willimott S, Baou M, Huf S, Deaglio S, Wagner SD (2007) Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4. Haematologica 92(10):1359-1366. doi: 10.3324/haematol.11340
123. Buggins AG, Levi A, Gohil S, Fishlock K, Patten PE, Calle Y, Yallop D, Devereux S (2011) Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9. Br J Haematol 154(2):216-222. doi: 10.1111/j.1365-2141.2011.08725.x
124. Redondo-Munoz J, Ugarte-Berzal E, Garcia-Marco JA, del Cerro MH, Van den Steen PE, Opdenakker G, Terol MJ, Garcia-Pardo A (2008) 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 112(1):169-178. doi: 10.1182/blood-2007-08-109249
125. Zucchetto A, Benedetti D, Tripodo C, Bomben R, Dal Bo M, Marconi D, Bossi F, Lorenzon D, Degan M, Rossi FM, Rossi D, Bulian P, Franco V, Del Poeta G, Deaglio S, Gaidano G, Tedesco F, Malavasi F, Gattei V (2009) CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphocytic leukemia cell survival. Cancer Res 69(9):4001-4009. doi: 10.1158/0008-5472.CAN-08-4173
126. Pearce L, Morgan L, Lin TT, Hewamana S, Matthews RJ, Deaglio S, Rowntree C, Fegan C, Pepper C, Brennan P (2010) Genetic modification of primary chronic lymphocytic leukemia cells with a lentivirus expressing CD38. Haematologica 95(3):514-517. doi: 10.3324/haematol.2009.014381
127. Mraz M, Zent CS, Church AK, Jelinek DF, Wu X, Pospisilova S, Ansell SM, Novak AJ, Kay NE, Witzig TE, Nowakowski GS (2011) Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alpha-4-beta-1 (VLA-4) with natalizumab can overcome this resistance. Br J Haematol 155(1):53-64. doi: 10.1111/j.1365-2141.2011.08794.x
128. Kiziltepe T, Ashley JD, Stefanick JF, Qi YM, Alves NJ, Handlogten MW, Suckow MA, Navari RM, Bilgicer B (2012) Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo. Blood Cancer J 2(4):e64. doi: 10.1038/bcj.2012.10
129. de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M (2012) The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood 119(11):2590-2594. doi: 10.1182/blood-2011-11-390989
130. Brown JR (2013) Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials. Curr Hematol Malignancy Rep 8(1):1-6. doi: 10.1007/s11899-012-0147-9
131. Castillo JJ, Furman M, Winer ES (2012) CAL-101: a phosphatidylinositol-3- kinase p110-delta inhibitor for the treatment of lymphoid malignancies. Exp Opin Investig Drugs 21(1):15-22. doi: 10.1517/13543784.2012.640318