ABSTRACT The tissue microenvironment in chronic lymphocytic leukemia (CLL) has an increasingly recognized role in disease progression, but the molecular mechanisms of cross talk between CLL

cells and their microenvironment remain incompletely defined. Bone marrow stromal cells (BMSC) protect CLL cells from apoptosis in a contact-dependent fashion, and have been used for the

identification of key pathways such as the CXCR4–CXCL12 axis. To further dissect the molecular impact of BMSC on survival and the molecular activation signature of CLL cells, we co-cultured

CLL cells with different BMSC. Gene expression profiling of CLL cells revealed that the lymphoid proto-oncogene _TCL1_ was among the top genes upregulated in CLL cells by BMSC. TCL1 mRNA and

role in the regulation of the known signaling enhancer and pro-survival molecule TCL1 in CLL. This provides a further rationale for therapeutically targeting the cross talk between CLL and

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support SIMILAR CONTENT BEING VIEWED BY OTHERS TUNING THE B-CLL MICROENVIRONMENT: EVIDENCE FOR BAG3 PROTEIN- MEDIATED REGULATION OF STROMAL FIBROBLASTS ACTIVITY Article Open access 28 August

2024 BONE MARROW STROMAL CELLS INDUCE CHROMATIN REMODELING IN MULTIPLE MYELOMA CELLS LEADING TO TRANSCRIPTIONAL CHANGES Article Open access 16 May 2024 THE MULTIPLE MYELOMA MICROENVIRONMENT

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combination with rituximab in patients with relapsed chronic lymphocytic leukemia. _Haematologica_ 2010; 95 (Suppl.2): (abstract 0772). Download references ACKNOWLEDGEMENTS This study was

supported by grants from the CLL Global Research Foundation (to WW, AR, MH and JAB) a Cancer Prevention and Research Institute of Texas (CPRIT) grant (to JAB), a DFG young investigator award

(HE3553/2-1, to MH), a Max-Eder Award by the Deutsche Krebshilfe (to MH) and the CECAD Initiative of Cologne University (to JMB and MH). AUTHOR CONTRIBUTIONS MS, EV and AB performed

CLL-BMSC co-cultures, RNA extraction, flow cytometry, immunoblots and immunoprecipitations, data analysis, and designed the figures and tables. EH performed the microarray studies and

-analysis and qRT-PCR. JMB performed the qRT-PCR, immunoblotting and miR expression analysis. MJK and WGW provided CLL samples and reviewed data and the manuscript. AR designed the

microarray studies and -analysis with JAB, and reviewed data and the manuscript. MH designed confirmatory experiments and reviewed data. JAB designed the research, supervised the study,

analyzed the data and wrote the paper with MS, EH, JMB, AR and MH. AUTHOR INFORMATION Author notes * M Sivina, E Hartmann, E Vasyutina and J M Boucas: These authors contributed equally to

this work. * M Herling and J A Burger: Co-corresponding authors. AUTHORS AND AFFILIATIONS * Department of Leukemia, Unit 428, The University of Texas MD Anderson Cancer Center, Houston, TX,

USA M Sivina, M J Keating, W G Wierda & J A Burger * Institute of Pathology, University of Würzburg, Würzburg, Germany E Hartmann & A Rosenwald * Department of Medicine 1, University

of Cologne, Cologne, Germany E Vasyutina, J M Boucas, A Breuer & M Herling Authors * M Sivina View author publications You can also search for this author inPubMed Google Scholar * E

Hartmann View author publications You can also search for this author inPubMed Google Scholar * E Vasyutina View author publications You can also search for this author inPubMed Google

Scholar * J M Boucas View author publications You can also search for this author inPubMed Google Scholar * A Breuer View author publications You can also search for this author inPubMed 

Google Scholar * M J Keating View author publications You can also search for this author inPubMed Google Scholar * W G Wierda View author publications You can also search for this author

inPubMed Google Scholar * A Rosenwald View author publications You can also search for this author inPubMed Google Scholar * M Herling View author publications You can also search for this

author inPubMed Google Scholar * J A Burger View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to M Herling or J A

Burger. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Leukemia website

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION (DOC 815 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sivina, M., Hartmann, E., Vasyutina, E.

_et al._ Stromal cells modulate TCL1 expression, interacting AP-1 components and TCL1-targeting micro-RNAs in chronic lymphocytic leukemia. _Leukemia_ 26, 1812–1820 (2012).

https://doi.org/10.1038/leu.2012.63 Download citation * Received: 09 March 2011 * Revised: 31 January 2012 * Accepted: 21 February 2012 * Published: 05 March 2012 * Issue Date: August 2012 *

DOI: https://doi.org/10.1038/leu.2012.63 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * TCL1 * marrow stromal cells * gene-expression profiling

* CLL