1 MMP-9 affects gene expression in chronic lymphocytic leukemia 2 revealing CD99 as an MMP-9 target and a novel partner in malignant cell 3 migration/arrest 4 Running title: Role of the MMP-9 target CD99 in CLL migration * * 5 Noemí Aguilera-Montilla1 , Elvira Bailón1 , Rebeca Uceda-Castro1, Estefanía 6 Ugarte-Berzal2, Andrea Santos1, Alejandra Gutiérrez-González1, Cristina 7 Pérez-Sánchez1, Philippe E. Van den Steen2, Ghislain Opdenakker2, José A. 8 García-Marco3 and Angeles García-Pardo1# 9 1Dept. of Molecular Biomedicine, Centro de Investigaciones Biológicas, 10 Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; 11 2Dept. of Microbiology and Immunology, Rega Institute for Medical Research, 12 University of Leuven, KU Leuven, Belgium; 3Dept. of Hematology, Hospital * 13 Universitario Puerta de Hierro, Madrid, Spain. These authors contributed 14 equally to this work. The authors declare no competing financial interests. 15 16 #Correspondence: Dr. Angeles García-Pardo, Dept. of Molecular Biomedicine, 17 Centro de Investigaciones Biológicas, CSIC. Ramiro de Maeztu 9, 28040 18 Madrid, Spain. Tel: 34-91-8373112ext 4430; e-mail: 19
[email protected] 20 Funding: Grants SAF2015-69180R and RD12/0036/0061 from the Ministry of 21 Economy and Competitivity (Spain), and S2010/BMD-2314 from the 22 Comunidad de Madrid/European Union (to AGP); Concerted Research 23 Actions C1 from KU Leuven (C16/17/010), and the Research Foundation of 24 Flander (FWO- Vlaanderen) (to EUB, PVdS and GO). 1 25 Abstract 26 We previously showed that MMP-9 contributes to CLL pathology by regulating 27 cell survival and migration and that, when present at high levels, MMP-9 28 induces cell arrest.