Stem Cells and Development The chronic lymphocytic leukemia clone disrupts the bone marrow microenvironment (doi: 10.1089/scd.2014.0229) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

Page 1 of 47

1 Title: THE CHRONIC LYMPHOCYTIC LEUKEMIA CLONE DISRUPTS THE BONE MARROW MICROENVIRONMENT

Authors: Alexandre JANEL1,2, Frédérique DUBOIS-GALOPIN3, Céline BOURGNE1, Juliette BERGER1, Karin TARTE4, Nathalie BOIRET-DUPRE1,2, Stéphane BOISGARD5, Pierre VERRELLE2, Pierre DECHELOTTE6, Olivier TOURNILHAC2,7 and Marc G. BERGER 1,2,7 1

Hematologie Biologique, CHU (University Hospital Center) Clermont-Fd, Hopital

Estaing, Clermont-Ferrand, France 2

EA7283 CREaT, Clermont Université, Université d’Auvergne, Clermont-Ferrand,

France 3

Laboratoire d’Hématologie, CHU (University Hospital Center) Purpan, Toulouse,

France 4

INSERM U917 – MICA, University of medicine, Rennes, France

5

Orthopédie Traumatologie, CHU (University Hospital Center) Clermont-Fd, hospital

Montpied, Clermont-Ferrand, France 6 7

Anatomie Pathologique, CHU Clermont-Fd, Hopital Estaing, Clermont-Ferrand, France Hématologie Clinique Adulte, CHU Clermont-Fd, Hopital Estaing, Clermont-

Ferrand, France Corresponding Author:

Prof. Marc G. BERGER (MD, PhD) Hématologie Biologique/Immunologie CHU Estaing, 1 place Lucie et Raymond Aubrac 63003 CLERMONT-FERRAND Cedex 1 France Tel: (33) 4 73 75 02 00 Fax: (33) 4 73 75 06 83 e-mail: [email protected]

Short running title: The B-CLL clone disrupts the BM microenvironment

Page 1 / 47

Stem Cells and Development The chronic lymphocytic leukemia clone disrupts the bone marrow microenvironment (doi: 10.1089/scd.2014.0229) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

Page 2 of 47

2

ACKNOWLEDGEMENTS/FUNDING The authors would like to thank Dominique Chadeyron for secretarial assistance, JeanJacques Guérin, Laurent Guillouard, Pascale Pigeon, Frédérique Lioret, Caroline Jamot, Nathalie Chaudagne, and Lucie Lafontaine, Clermont-Ferrand University Hospital, for technical assistance, the staff from the Centre de Ressources Biologiques (CRB) Auvergne for cryopreserving human samples and Lemlih Ouchchane for participating in statistical analysis. This work was supported by grants from the ComitéDépartemental (Puy-de-Dôme) de la Ligue Contre le Cancer [Anti-Cancer League Regional Committee (Puy-de-Dôme, France)] and the Association Laurette Fugain, France. Word count of abstract: 235 Word count of text: 4683 Figure/Table count: 5 Reference count: 52

Page 2 / 47

Stem Cells and Development The chronic lymphocytic leukemia clone disrupts the bone marrow microenvironment (doi: 10.1089/scd.2014.0229) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

Page 3 of 47

3

ABSTRACT

The systematic localization of chronic lymphocytic leukemia (CLL) B-cells in the bone marrow (BM), together with the ex vivo protective effect of stromal cells on their spontaneous apoptosis, both indicate a specific role of the BM microenvironment. In vivo, the impact of CLL cells on mesenchymal stromal cells (MSC) remains a source of debate. Here, we quantified and expanded colony forming unit-fibroblasts (CFU-F) from CLL-BM under standard conditions, analyzed the expression of selected genes and studied secretion profiles. We observed failing of CLL-BM cultures in standard conditions (45.5% vs. 1.2 and a P-value ≤ 0.05; and (ii) Significance Analysis of Microarrays software, using 1000 permutations, a fold change (FC) >1.2 or

The chronic lymphocytic leukemia clone disrupts the bone marrow microenvironment.

The systematic localization of chronic lymphocytic leukemia (CLL) B-cells in the bone marrow (BM), together with the ex vivo protective effect of stro...
915KB Sizes 0 Downloads 4 Views