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Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1

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  1. 1

    Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011; 475: 101–105.

    CAS  Article  Google Scholar 

  2. 2

    Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2012; 44: 47–52.

    CAS  Article  Google Scholar 

  3. 3

    Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011; 365: 2497–2506.

    CAS  Article  Google Scholar 

  4. 4

    Damm F, Mylonas E, Cosson A, Yoshida K, Della Valle V, Mouly E et al. Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov 2014; 4: 1088–1101.

    CAS  Article  Google Scholar 

  5. 5

    Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910–1916.

    CAS  Article  Google Scholar 

  6. 6

    Bea S, Lopez-Guillermo A, Ribas M, Puig X, Pinyol M, Carrio A et al. Genetic imbalances in progressed B-cell chronic lymphocytic leukemia and transformed large-cell lymphoma (Richter's syndrome). Am J Pathol 2002; 161: 957–968.

    CAS  Article  Google Scholar 

  7. 7

    Schwaenen C, Nessling M, Wessendorf S, Salvi T, Wrobel G, Radlwimmer B et al. Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations. Proc Natl Acad Sci USA 2004; 101: 1039–1044.

    CAS  Article  Google Scholar 

  8. 8

    Pfeifer D, Pantic M, Skatulla I, Rawluk J, Kreutz C, Martens UM et al. Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood 2007; 109: 1202–1210.

    CAS  Article  Google Scholar 

  9. 9

    Chapiro E, Leporrier N, Radford-Weiss I, Bastard C, Mossafa H, Leroux D et al. Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages. Leuk Res 2010; 34: 63–68.

    CAS  Article  Google Scholar 

  10. 10

    Rinaldi A, Mian M, Kwee I, Rossi D, Deambrogi C, Mensah AA et al. Genome-wide DNA profiling better defines the prognosis of chronic lymphocytic leukaemia. Br J Haematol 2011; 154: 590–599.

    Article  Google Scholar 

  11. 11

    Edelmann J, Holzmann K, Miller F, Winkler D, Buhler A, Zenz T et al. High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations. Blood 2012; 120: 4783–4794.

    CAS  Article  Google Scholar 

  12. 12

    Lapalombella R, Sun Q, Williams K, Tangeman L, Jha S, Zhong Y et al. Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia. Blood 2012; 120: 4621–4634.

    CAS  Article  Google Scholar 

  13. 13

    Sutton L, Chevret S, Tournilhac O, Divine M, Leblond V, Corront B et al. Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC. Blood 2011; 117: 6109–6119.

    CAS  Article  Google Scholar 

  14. 14

    Turner JG, Dawson J, Sullivan DM . Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol 2012; 83: 1021–1032.

    CAS  Article  Google Scholar 

  15. 15

    Landau DA, Tausch E, Taylor-Weiner AN, Stewart C, Reiter JG, Bahlo J et al. Mutations driving CLL and their evolution in progression and relapse. Nature 2015; 526: 525–530.

    CAS  Article  Google Scholar 

  16. 16

    Zhong Y, El-Gamal D, Dubovsky JA, Beckwith KA, Harrington BK, Williams KE et al. Selinexor suppresses downstream effectors of B-cell activation, proliferation and migration in chronic lymphocytic leukemia cells. Leukemia 2014; 28: 1158–1163.

    CAS  Article  Google Scholar 

  17. 17

    Lepretre S, Aurran T, Mahe B, Cazin B, Tournilhac O, Maisonneuve H et al. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial. Blood 2012; 119: 5104–5110.

    CAS  Article  Google Scholar 

  18. 18

    Jeromin S, Weissmann S, Haferlach C, Dicker F, Bayer K, Grossmann V et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia 2014; 28: 108–117.

    CAS  Article  Google Scholar 

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We thank the Centre de Ressource Biologique de Caen for Lepretre’s trial samples. We are also grateful to O Bernard for critical comments, X Troussard, R Guieze, S Struski, E Fonteneau, R Delepine, O Kosmider, D Bouscary, C Delacroix and L Cabon for invaluable help, and LY Sebaert for the gift of the JVM-3 cell line. OSU-CLL cells were provided by The Ohio State University’s Human Genetics Sample Bank. This work was supported by Roche Diagnostics, the Association Laurette Fugain (ALF10/09, ALF14/08 and ALF 15/09), Ligue Contre le Cancer (RS15/75-63 and RS16/75-50) and Fondation ARC (Association pour la Recherche sur le Cancer) (SFI20111203530 and PJA20151203407). AC holds PhD fellowships from Fondation pour la Recherche Medicale (FDT20140931078) and Société Française d’Hématologie.

Author contributions

AC conceived and performed experimental work, analyzed the data, and helped to write the manuscript. EC, NB, H-AC, CA, CG, LH and M-NB-N conceived, and performed experimental work and analyzed the data. FD, HM-B, SC, MU, VM, VL, KM, SL, PF, LS, MLG-T enrolled patients and managed CLL samples. JL, CL, JLe performed statistical analysis. YL provided selinexor and KPT-301. SAS and FN-K conceived and supervised the project, designed experiments, interpreted the data and wrote the manuscript.

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Corresponding authors

Correspondence to S A Susin or F Nguyen-Khac.

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Competing interests

YL is an employee of Karyopharm Therapeutics Inc. and receives compensation, and holds equity in the company. The remaining authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Cosson, A., Chapiro, E., Bougacha, N. et al. Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1. Leukemia 31, 1625–1629 (2017).

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