The genomic landscape of chronic lymphocytic leukaemia: Biological and clinical implications

British Journal of Haematology

Volumn 169, Issue 1, 2015, Pages 14-31

  Strefford, Jonathan C ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Chronic lymphocytic leukaemia; Clinical aspects; Genetic analysis; Prognostic factors

Indexed keywords

ATM PROTEIN; CHLORAMBUCIL; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB; LENALIDOMIDE; NOTCH1 RECEPTOR; OBINUTUZUMAB; RITUXIMAB;

ATM GENE; CANCER CHEMOTHERAPY; CANCER PROGNOSIS; CANCER RESISTANCE; CELL CYCLE REGULATION; CHROMOSOME ABERRATION; CHRONIC LYMPHATIC LEUKEMIA; CLONAL EVOLUTION; COPY NUMBER VARIATION; DNA DAMAGE; GENE MUTATION; GENOMICS; HUMAN; IMMUNOGLOBULIN HEAVY CHAIN GENE; IMMUNOGLOBULIN VARIABLE REGION; INTERSTITIAL CHROMOSOME DELETION; LEUKEMIA RELAPSE; LEUKEMIA REMISSION; LYMPHOMA; MALIGNANT TRANSFORMATION; MOLECULAR PATHOLOGY; MONOCLONAL B CELL LYMPHOCYTOSIS; NEXT GENERATION SEQUENCING; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; RICHTER SYNDROME; RNA PROCESSING; SURVIVAL RATE; SURVIVAL TIME; TELOMERE; TRISOMY 12; TUMOR SUPPRESSOR GENE; GENETICS; GENOMIC INSTABILITY; HUMAN GENOME; PATHOLOGY;

GENOME, HUMAN; GENOMIC INSTABILITY; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL;

EID: 84925131469     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.13254     Document Type: Review

References (131)

1. Abrisqueta, P., Pereira, A., Rozman, C., Aymerich, M., Giné, E., Moreno, C., Muntañola, A., Rozman, M., Villamor, N., Hodgson, K., Campo, E., Bosch, F. & Montserrat, E. (2009) Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the Hospital Clinic of Barcelona experience. Blood, 114, 2044-2050.
2. Arruga, F., Gizdic, B., Serra, S., Vaisitti, T., Ciardullo, C., Coscia, M., Laurenti, L., D'Arena, G., Jaksic, O., Inghirami, G., Rossi, D., Gaidano, G. & Deaglio, S. (2014) Functional impact of NOTCH1 mutations in chronic lymphocytic leukemia. Leukemia, 28, 1060-1070.
3. Augereau, A., T'kint de Roodenbeke, C., Simonet, T., Bauwens, S., Horard, B., Callanan, M., Leroux, D., Jallades, L., Salles, G., Gilson, E. & Poncet, D. (2011) Telomeric damage in early stage of chronic lymphocytic leukemia correlates with shelterin dysregulation. Blood, 118, 1316-1322.
4. Austen, B., Skowronska, A., Baker, C., Powell, J.E., Gardiner, A., Oscier, D., Majid, A., Dyer, M., Siebert, R., Taylor, A.M., Moss, P.A. & Stankovic, T. (2007) Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. Journal of Clinical Oncology, 25, 5448-5457.
5. Badoux, X.C., Keating, M.J., Wen, S., Wierda, W.G., O'Brien, S.M., Faderl, S., Sargent, R., Burger, J.A. & Ferrajoli, A. (2013) Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. Journal of Clinical Oncology, 31, 584-591.
6. Balatti, V., Bottoni, A., Palamarchuk, A., Alder, H., Rassenti, L.Z., Kipps, T.J., Pekarsky, Y. & Croce, C.M. (2011) NOTCH1 mutations in CLL associated with trisomy 12. Blood, 119, 329-331.
7. Baliakas, P., Hadzidimitriou, A., Sutton, L.A., Rossi, D., Minga, E., Villamor, N., Larrayoz, M., Kminkova, J., Agathangelidis, A., Davis, Z., Tausch, E., Stalika, E., Kantorova, B., Mansouri, L., Scarfò, L., Cortese, D., Navrkalova, V., Rose-Zerilli, M.J., Smedby, K.E., Juliusson, G., Anagnostopoulos, A., Makris, A.M., Navarro, A., Delgado, J., Oscier, D., Belessi, C., Stilgenbauer, S., Ghia, P., Pospisilova, S., Gaidano, G., Campo, E., Strefford, J.C., Stamatopoulos, K. & Rosenquist, R. (2014) Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia, DOI: 10.1038/leu.2014.196 [Epub ahead of print].
8. Bechter, O.E., Eisterer, W., Pall, G., Hilbe, W., Kühr, T. & Thaler, J. (1998) Telomere length and telomerase activity predict survival in patients with B cell chronic lymphocytic leukemia. Cancer Research, 58, 4918-4922.
9. Best, O.G., Gardiner, A.C., Davis, Z.A., Tracy, I., Ibbotson, R.E., Majid, A., Dyer, M.J. & Oscier, D.G. (2008) A novel functional assay using etoposide plus nutlin-3a detects and distinguishes between ATM and TP53 mutations in CLL. Leukemia, 22, 1456-1459.
10. Binet, J.L., 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, M.T., Monconduit, M., Belabbes, S. & Gremy, F. (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, 48, 198-206.
11. Britt-Compton, B., Lin, T.T., Ahmed, G., Weston, V., Jones, R.E., Fegan, C., Oscier, D.G., Stankovic, T., Pepper, C. & Baird, D.M. (2012) Extreme telomere erosion in ATM-mutated and 11q-deleted CLL patients is independent of disease stage. Leukemia, 26, 826-830.
12. Byrd, J.C., Furman, R.R., Coutre, S.E., Flinn, I.W., Burger, J.A., Blum, K.A., Grant, B., Sharman, J.P., Coleman, M., Wierda, W.G., Jones, J.A., Zhao, W., Heerema, N.A., Johnson, A.J., Sukbuntherng, J., Chang, B.Y., Clow, F., Hedrick, E., Buggy, J.J., James, D.F. & O'Brien, S.M. (2013) Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. The New England Journal of Medicine, 369, 32-42.
13. Catovsky, D., Richards, S., Matutes, E., Oscier, D., Dyer, M.J., Bezares, R.F., Pettitt, A.R., Hamblin, T., Milligan, D.W., Child, J.A., Hamilton, M.S., Dearden, C.E., Smith, A.G., Bosanquet, A.G., Davis, Z., Brito-Babapulle, V., Else, M., Wade, R., Hillmen, P., National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group & NCRI Chronic Lymphocytic Leukaemia Working Group (2007) Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet, 370, 230-239.
14. Chapiro, E., Leporrier, N., Radford-Weiss, I., Bastard, C., Mossafa, H., Leroux, D., Tigaud, I., De Braekeleer, M., Terré, C., Brizard, F., Callet-Bauchu, E., Struski, S., Veronese, L., Fert-Ferrer, S., Taviaux, S., Lesty, C., Davi, F., Merle-Béral, H., Bernard, O.A., Sutton, L., Raynaud, S.D. & Nguyen-Khac, F. (2010) Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages. Leukemia Research, 34, 63-68.
15. Chigrinova, E., Rinaldi, A., Kwee, I., Rossi, D., Rancoita, P.M., Strefford, J.C., Oscier, D., Stamatopoulos, K., Papadaki, T., Berger, F., Young, K.H., Murray, F., Rosenquist, R., Greiner, T.C., Chan, W.C., Orlandi, E.M., Lucioni, M., Marasca, R., Inghirami, G., Ladetto, M., Forconi, F., Cogliatti, S., Votavova, H., Swerdlow, S.H., Stilgenbauer, S., Piris, M.A., Matolcsy, A., Spagnolo, D., Nikitin, E., Zamò, A., Gattei, V., Bhagat, G., Ott, G., Zucca, E., Gaidano, G. & Bertoni, F. (2013) Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood, 122, 2673-2682.
16. Chiorazzi, N., Rai, K.R. & Ferrarini, M. (2005) Chronic lymphocytic leukemia. New England Journal of Medicine, 352, 804-815.
17. Clifford, R., Louis, T., Robbe, P., Ackroyd, S., Burns, A., Timbs, A.T., Wright Colopy, G., Dreau, H., Sigaux, F., Judde, J.G., Rotger, M., Telenti, A., Lin, Y.L., Pasero, P., Maelfait, J., Titsias, M., Cohen, D.R., Henderson, S.J., Ross, M.T., Bentley, D., Hillmen, P., Pettitt, A., Rehwinkel, J., Knight, S.J., Taylor, J.C., Crow, Y.J., Benkirane, M. & Schuh, A. (2014) SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. Blood, 123, 1021-1031.
18. Cosson, A., Chapiro, E., Belhouachi, N., Cung, H.A., Keren, B., Damm, F., Algrin, C., Lefebvre, C., Fert-Ferrer, S., Luquet, I., Gachard, N., Mugneret, F., Terre, C., Collonge-Rame, M.A., Michaux, L., Rafdord-Weiss, I., Talmant, P., Veronese, L., Nadal, N., Struski, S., Barin, C., Helias, C., Lafage, M., Lippert, E., Auger, N., Eclache, V., Roos-Weil, D., Leblond, V., Settegrana, C., Maloum, K., Davi, F., Merle-Beral, H., Lesty, C., Nguyen-Khac, F. & Groupe Francophone de Cytogénétique Hématologique (2014) 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma. Genes Chromosomes Cancer, 53, 657-666.
19. Crasta, K., Ganem, N.J., Dagher, R., Lantermann, A.B., Ivanova, E.V., Pan, Y., Nezi, L., Protopopov, A., Chowdhury, D. & Pellman, D. (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature, 482, 53-58.
20. Damle, R.N., Wasil, T., Fais, F., Ghiotto, F., Valetto, A., Allen, S.L., Buchbinder, A., Budman, D., Dittmar, K., Kolitz, J., Lichtman, S.M., Schulman, P., Vinciguerra, V.P., Rai, K.R., Ferrarini, M. & Chiorazzi, N. (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood, 94, 1840-1847.
21. Damle, R.N., Batliwalla, F.M., Ghiotto, F., Valetto, A., Albesiano, E., Sison, C., Allen, S.L., Kolitz, J., Vinciguerra, V.P., Kudalkar, P., Wasil, T., Rai, K.R., Ferrarini, M., Gregersen, P.K. & Chiorazzi, N. (2004) Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood, 103, 375-382.
22. Damm, F., Mylonas, E., Cosson, A., Yoshida, K., Della Valle, V., Mouly, E., Diop, M., Scourzic, L., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Kikushige, Y., Davi, F., Lambert, J., Gautheret, D., Merle-Béral, H., Sutton, L., Dessen, P., Solary, E., Akashi, K., Vainchenker, W., Mercher, T., Droin, N., Ogawa, S., Nguyen-Khac, F. & Bernard, O.A. (2014) Acquired initiating mutations in early hematopoietic cells of cll patients. Cancer Discovery, 4, 1088-1101.
23. de Paoli, L., Cerri, M., Monti, S., Rasi, S., Spina, V., Bruscaggin, A., Greco, M., Ciardullo, C., Famà, R., Cresta, S., Maffei, R., Ladetto, M., Martini, M., Laurenti, L., Forconi, F., Marasca, R., Larocca, L.M., Bertoni, F., Gaidano, G. & Rossi, D. (2013) MGA, a suppressor of MYC, is recurrently inactivated in high risk chronic lymphocytic leukemia. Leukaemia & Lymphoma, 54, 1987-1990.
24. Delgado, J., Salaverria, I., Baumann, T., Martinez-Trillos, A., Lee, E., Jimenez, L., Navarro, A., Royo, C., Santacruz, R., Lopez, C., Payer, A.R., Colado, E., Gonzalez, M., Armengol, L., Colomer, D., Pinyol, M., Villamor, N., Aymerich, M., Carrió, A., Costa, D., Clot, G., Gine', E., López-Guillermo, A., Campo, E. & Beà, S. (2014) Genomic complexity and IGHV mutational status are key predictors of outcome of chronic lymphocytic leukemia patients with TP53 disruption. Haematologica, 99, e231-e234.
25. Deneberg, S., Kanduri, M., Ali, D., Bengtzen, S., Karimi, M., Qu, Y., Kimby, E., Mansouri, L., Rosenquist, R., Lennartsson, A. & Lehmann, S. (2014) microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia. Epigenetics, 9, 910-917.
26. Di Ianni, M., Baldoni, S., Rosati, E., Ciurnelli, R., Cavalli, L., Martelli, M.F., Marconi, P., Screpanti, I. & Falzetti, F. (2009) A new genetic lesion in B-CLL: a NOTCH1 PEST domain mutation. British Journal of Haematology, 146, 689-691.
27. Dicker, F., Herholz, H., Schnittger, S., Nakao, A., Patten, N., Wu, L., Kern, W., Haferlach, T. & Haferlach, C. (2009) The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype. Leukemia, 23, 117-124.
28. Dierlamm, J., Wlodarska, I., Michaux, L., Vermeesch, J.R., Meeus, P., Stul, M., Criel, A., Verhoef, G., Thomas, J., Delannoy, A., Louwagie, A., Cassiman, J.J., Mecucci, C., Hagemeijer, A. & Van den Berghe, H. (1997) FISH identifies different types of duplications with 12q13-15 as the commonly involved segment in B-cell lymphoproliferative malignancies characterized by partial trisomy 12. Genes Chromosomes Cancer, 20, 113-119.
29. Döhner, H., Fischer, K., Bentz, M., Hansen, K., Benner, A., Cabot, G., Diehl, D., Schlenk, R., Coy, J., Stilgenbauer, S., Volkmann, M., Galle, P.R., Poustka, A., Hunstein, W. & Lichter, P. (1995) p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood, 85, 1580-1589.
30. Döhner, H., Stilgenbauer, S., James, M.R., Benner, A., Weilguni, T., Bentz, M., Fischer, K., Hunstein, W. & Lichter, P. (1997) 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood, 89, 2516-2522.
31. Döhner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Kröber, A., Bullinger, L., Döhner, K., Bentz, M. & Lichter, P. (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. New England Journal of Medicine, 343, 1910-1916.
32. Edelmann, J., Holzmann, K., Miller, F., Winkler, D., Bühler, A., Zenz, T., Bullinger, L., Kühn, M.W., Gerhardinger, A., Bloehdorn, J., Radtke, I., Su, X., Ma, J., Pounds, S., Hallek, M., Lichter, P., Korbel, J., Busch, R., Mertens, D., Downing, J.R., Stilgenbauer, S. & Döhner, H. (2012) High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations. Blood, 120, 4783-4794.
33. Fabbri, G., Rasi, S., Rossi, D., Trifonov, V., Khiabanian, H., Ma, J., Grunn, A., Fangazio, M., Capello, D., Monti, S., Cresta, S., Gargiulo, E., Forconi, F., Guarini, A., Arcaini, L., Paulli, M., Laurenti, L., Larocca, L.M., Marasca, R., Gattei, V., Oscier, D., Bertoni, F., Mullighan, C.G., Foá, R., Pasqualucci, L., Rabadan, R., Dalla-Favera, R. & Gaidano, G. (2011) Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. Journal of Experimental Medicine, 208, 1389-1401.
34. Fabbri, G., Khiabanian, H., Holmes, A.B., Wang, J., Messina, M., Mullighan, C.G., Pasqualucci, L., Rabadan, R. & Dalla-Favera, R. (2013) Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome. Journal of Experimental Medicine, 210, 2273-2288.
35. Ferrajoli, A., Lee, B.N., Schlette, E.J., O'Brien, S.M., Gao, H., Wen, S., Wierda, W.G., Estrov, Z., Faderl, S., Cohen, E.N., Li, C., Reuben, J.M. & Keating, M.J. (2008) Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood, 111, 5291-5297.
36. Ferreira, P.G., Jares, P., Rico, D., Gómez-López, G., Martínez-Trillos, A., Villamor, N., Ecker, S., González-Pérez, A., Knowles, D.G., Monlong, J., Johnson, R., Quesada, V., Djebali, S., Papasaikas, P., López-Guerra, M., Colomer, D., Royo, C., Cazorla, M., Pinyol, M., Clot, G., Aymerich, M., Rozman, M., Kulis, M., Tamborero, D., Gouin, A., Blanc, J., Gut, M., Gut, I., Puente, X.S., Pisano, D.G., Martin-Subero, J.I., López-Bigas, N., López-Guillermo, A., Valencia, A., López-Otín, C., Campo, E. & Guigó, R. (2014) Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia. Genome Research, 24, 212-226.
37. Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W.B., Fedorov, O., Morse, E.M., Keates, T., Hickman, T.T., Felletar, I., Philpott, M., Munro, S., McKeown, M.R., Wang, Y., Christie, A.L., West, N., Cameron, M.J., Schwartz, B., Heightman, T.D., La Thangue, N., French, C.A., Wiest, O., Kung, A.L., Knapp, S. & Bradner, J.E. (2010) Selective inhibition of BET bromodomains. Nature, 468, 1067-1073.
38. Fitchett, M., Griffiths, M.J., Oscier, D.G., Johnson, S. & Seabright, M. (1987) Chromosome abnormalities involving band 13q14 in hematologic malignancies. Cancer Genetics and Cytogenetics, 24, 143-150.
39. Furman, R.R., Sharman, J.P., Coutre, S.E., Cheson, B.D., Pagel, J.M., Hillmen, P., Barrientos, J.C., Zelenetz, A.D., Kipps, T.J., Flinn, I., Ghia, P., Eradat, H., Ervin, T., Lamanna, N., Coiffier, B., Pettitt, A.R., Ma, S., Stilgenbauer, S., Cramer, P., Aiello, M., Johnson, D.M., Miller, L.L., Li, D., Jahn, T.M., Dansey, R.D., Hallek, M. & O'Brien, S.M. (2014) Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. The New England Journal of Medicine, 370, 997-1007.
40. Gahrton, G., Robèrt, K.H., Friberg, K., Zech, L. & Bird, A.G. (1980a) Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation. Blood, 56, 640-647.
41. Gahrton, G., Robèrt, K.H., Friberg, K., Zech, L. & Bird, A.G. (1980b) Extra chromosome 12 in chronic lymphocytic leukaemia. Lancet, 2, 146-147.
42. Gaidano, G., Ballerini, P., Gong, J.Z., Inghirami, G., Neri, A., Newcomb, E.W., Magrath, I.T., Knowles, D.M. & Dalla-Favera, R. (1991) p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 88, 5413-5417.
43. Garding, A., Bhattacharya, N., Claus, R., Ruppel, M., Tschuch, C., Filarsky, K., Idler, I., Zucknick, M., Caudron-Herger, M., Oakes, C., Fleig, V., Keklikoglou, I., Allegra, D., Serra, L., Thakurela, S., Tiwari, V., Weichenhan, D., Benner, A., Radlwimmer, B., Zentgraf, H., Wiemann, S., Rippe, K., Plass, C., Döhner, H., Lichter, P., Stilgenbauer, S. & Mertens, D. (2013) Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the In Cis downregulation of a gene cluster that targets NF-kB. PLoS Genetics, 9, e1003373.
44. Goede, V., Fischer, K., Busch, R., Engelke, A., Eichhorst, B., Wendtner, C.M., Chagorova, T., de la Serna, J., Dilhuydy, M.S., Illmer, T., Opat, S., Owen, C.J., Samoylova, O., Kreuzer, K.A., Stilgenbauer, S., Döhner, H., Langerak, A.W., Ritgen, M., Kneba, M., Asikanius, E., Humphrey, K., Wenger, M. & Hallek, M. (2014) Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. The New England Journal of Medicine, 270, 1101-1110.
45. Gonzalez, D., Martinez, P., Wade, R., Hockley, S., Oscier, D., Matutes, E., Dearden, C.E., Richards, S.M., Catovsky, D. & Morgan, G.J. (2011) Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. Journal of Clinical Oncology, 29, 2223-2229.
46. Grabowski, P., Hultdin, M., Karlsson, K., Tobin, G., Aleskog, A., Thunberg, U., Laurell, A., Sundström, C., Rosenquist, R. & Roos, G. (2005) Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood, 105, 4807-4812.
47. Grandori, C., Cowley, S.M., James, L.P. & Eisenman, R.N. (2000) The Myc/Max/Mad network and the transcriptional control of cell behavior. Annual Review of Cell and Developmental Biology, 16, 653-699.
48. Greaves, M. & Maley, C.C. (2012) Clonal evolution in cancer. Nature, 481, 306-313.
49. Gunnarsson, R., Staaf, J., Jansson, M., Ottesen, A.M., Göransson, H., Liljedahl, U., Ralfkiaer, U., Mansouri, M., Buhl, A.M., Smedby, K.E., Hjalgrim, H., Syvänen, A.C., Borg, A., Isaksson, A., Jurlander, J., Juliusson, G. & Rosenquist, R. (2008) Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia-a comparative study of four differently designed, high resolution microarray platforms. Genes Chromosomes Cancer, 47, 697-711.
50. Gunnarsson, R., Isaksson, A., Mansouri, M., Göransson, H., Jansson, M., Cahill, N., Rasmussen, M., Staaf, J., Lundin, J., Norin, S., Buhl, A.M., Smedby, K.E., Hjalgrim, H., Karlsson, K., Jurlander, J., Juliusson, G. & Rosenquist, R. (2010) Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients. Leukemia, 24, 211-215.
51. Haferlach, C., Dicker, F., Schnittger, S., Kern, W. & Haferlach, T. (2007) Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. Leukemia, 21, 2442-2451.
52. Hallek, M., Fischer, K., Fingerle-Rowson, G., Fink, A.M., Busch, R., Mayer, J., Hensel, M., Hopfinger, G., Hess, G., von Grünhagen, U., Bergmann, M., Catalano, J., Zinzani, P.L., Caligaris-Cappio, F., Seymour, J.F., Berrebi, A., Jäger, U., Cazin, B., Trneny, M., Westermann, A., Wendtner, C.M., Eichhorst, B.F., Staib, P., Bühler, A., Winkler, D., Zenz, T., Böttcher, S., Ritgen, M., Mendila, M., Kneba, M., Döhner, H., Stilgenbauer, S., International Group of Investigators & German Chronic Lymphocytic Leukaemia Study Group (2010) Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet, 376, 1164-1174.
53. Hamblin, T.J., Davis, Z., Gardiner, A., Oscier, D.G. & Stevenson, F.K. (1999) Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94, 1848-1854.
54. Havelange, V., Pekarsky, Y., Nakamura, T., Palamarchuk, A., Alder, H., Rassenti, L., Kipps, T. & Croce, C.M. (2011) IRF4 mutations in chronic lymphocytic leukemia. Blood, 118, 2827-2829.
55. Hurley, J.N., Fu, S.M., Kunkel, H.G., Chaganti, R.S. & German, J. (1980) Chromosome abnormalities of leukaemic B lymphocytes in chronic lymphocytic leukaemia. Nature, 283, 76-78.
56. Jeromin, S., Weissmann, S., Haferlach, C., Dicker, F., Bayer, K., Grossmann, V., Alpermann, T., Roller, A., Kohlmann, A., Haferlach, T., Kern, W. & Schnittger, S. (2014) SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia, 28, 108-117.
57. Klein, U., Lia, M., Crespo, M., Siegel, R., Shen, Q., Mo, T., Ambesi-Impiombato, A., Califano, A., Migliazza, A., Bhagat, G. & Dalla-Favera, R. (2010) The DLEU2/miR-15a/16-1 Cluster Controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell, 17, 28-40.
58. Kujawski, L., Ouillette, P., Erba, H., Saddler, C., Jakubowiak, A., Kaminski, M., Shedden, K. & Malek, S.N. (2008) Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood, 112, 1993-2003.
59. Kulis, M., Heath, S., Bibikova, M., Queirós, A.C., Navarro, A., Clot, G., Martínez-Trillos, A., Castellano, G., Brun-Heath, I., Pinyol, M., Barberán-Soler, S., Papasaikas, P., Jares, P., Beà, S., Rico, D., Ecker, S., Rubio, M., Royo, R., Ho, V., Klotzle, B., Hernández, L., Conde, L., López-Guerra, M., Colomer, D., Villamor, N., Aymerich, M., Rozman, M., Bayes, M., Gut, M., Gelpí, J.L., Orozco, M., Fan, J.B., Quesada, V., Puente, X.S., Pisano, D.G., Valencia, A., López-Guillermo, A., Gut, I., López-Otín, C., Campo, E. & Martín-Subero, J.I. (2012) Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nature Genetics, 44, 1236-1242.
60. Landau, D.A., Carter, S.L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M.S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., Wan, Y., Zhang, W., Shukla, S.A., Vartanov, A., Fernandes, S.M., Saksena, G., Cibulskis, K., Tesar, B., Gabriel, S., Hacohen, N., Meyerson, M., Lander, E.S., Neuberg, D., Brown, J.R., Getz, G. & Wu, C.J. (2013) Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell, 152, 714-726.
61. Lia, M., Carette, A., Tang, H., Shen, Q., Mo, T., Bhagat, G., Dalla-Favera, R. & Klein, U. (2011) Functional dissection of the chromosome 13q14 tumor-suppressor locus using transgenic mouse lines. Blood, 119, 2981-2990.
62. Lin, T.T., Letsolo, B.T., Jones, R.E., Rowson, J., Pratt, G., Hewamana, S., Fegan, C., Pepper, C. & Baird, D.M. (2010a) Telomere dysfunction and fusion during the progression of chronic lymphocytic leukemia: evidence for a telomere crisis. Blood, 116, 1899-1907.
63. Lin, S.C., Lo, Y.C. & Wu, H. (2010b) Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature, 465, 885-890.
64. López, C., Delgado, J., Costa, D., Conde, L., Ghita, G., Villamor, N., Navarro, A., Cazorla, M., Gómez, C., Arias, A., Muñoz, C., Baumann, T., Rozman, M., Aymerich, M., Colomer, D., Cobo, F., Campo, E., López-Guillermo, A., Montserrat, E. & Carrió, A. (2012) Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations. Genes Chromosomes Cancer, 51, 881-889.
65. López-Guerra, M., Xargay-Torrent, S., Rosich, L., Montraveta, A., Roldán, J., Matas-Céspedes, A., Villamor, N., Aymerich, M., López-Otín, C., Pérez-Galán, P., Roué, G., Campo, E. & Colomer, D. (2014) The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells. Leukemia, DOI: 10.1038/leu.2014.143 [Epub ahead of print].
66. Martínez-Trillos, A., Pinyol, M., Navarro, A., Aymerich, M., Jares, P., Juan, M., Rozman, M., Colomer, D., Delgado, J., Giné, E., González-Díaz, M., Hernández-Rivas, J.M., Colado, E., Rayón, C., Payer, A.R., Terol, M.J., Navarro, B., Quesada, V., Puente, X.S., Rozman, C., López-Otín, C., Campo, E., López-Guillermo, A. & Villamor, N. (2014) Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome. Blood, 123, 37909-37906.
67. Matutes, E., Oscier, D., Garcia-Marco, J., Ellis, J., Copplestone, A., Gillingham, R., Hamblin, T., Lens, D., Swansbury, G.J. & Catovsky, D. (1996) Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. British Journal of Haematology, 92, 382-388.
68. Messina, M., Del Giudice, I., Khiabanian, H., Rossi, D., Chiaretti, S., Rasi, S., Spina, V., Holmes, A.B., Marinelli, M., Fabbri, G., Piciocchi, A., Mauro, F.R., Guarini, A., Gaidano, G., Dalla-Favera, R., Pasqualucci, L., Rabadan, R. & Foà, R. (2014) Genetic lesions associated with chronic lymphocytic leukemia chemo-refractoriness. Blood, 123, 2378-2388.
69. Messmer, B.T., Messmer, D., Allen, S.L., Kolitz, J.E., Kudalkar, P., Cesar, D., Murphy, E.J., Koduru, P., Ferrarini, M., Zupo, S., Cutrona, G., Damle, R.N., Wasil, T., Rai, K.R., Hellerstein, M.K. & Chiorazzi, N. (2005) In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. The Journal of Clinical Investigation, 115, 755-764.
70. Morschhauser, F. (2009) Phase I Study of RO5072759 (GA101) in relapsed/refractory chronic lymphocytic leukemia. Blood, 114, 884.
71. Nik-Zainal, S., Alexandrov, L.B., Wedge, D.C., Van Loo, P., Greenman, C.D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L.A., Menzies, A., Martin, S., Leung, K., Chen, L., Leroy, C., Ramakrishna, M., Rance, R., Lau, K.W., Mudie, L.J., Varela, I., McBride, D.J., Bignell, G.R., Cooke, S.L., Shlien, A., Gamble, J., Whitmore, I., Maddison, M., Tarpey, P.S., Davies, H.R., Papaemmanuil, E., Stephens, P.J., McLaren, S., Butler, A.P., Teague, J.W., Jönsson, G., Garber, J.E., Silver, D., Miron, P., Fatima, A., Boyault, S., Langerød, A., Tutt, A., Martens, J.W., Aparicio, S.A., Borg, Å., Salomon, A.V., Thomas, G., Børresen-Dale, A.L., Richardson, A.L., Neuberger, M.S., Futreal, P.A., Campbell, P.J., Stratton, M.R. & Breast Cancer Working Group of the International Cancer Genome Consortium (2012) Mutational processes molding the genomes of 21 breast cancers. Cell, 149, 979-993.
72. O'Brien, S., Furman, R.R., Coutre, S.E., Sharman, J.P., Burger, J.A., Blum, K.A., Grant, B., Richards, D.A., Coleman, M., Wierda, W.G., Jones, J.A., Zhao, W., Heerema, N.A., Johnson, A.J., Izumi, R., Hamdy, A., Chang, B.Y., Graef, T., Clow, F., Buggy, J.J., James, D.F. & Byrd, J.C. (2014) Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. The Lancet. Oncology, 15, 48-58.
73. Ojha, J., Secreto, C., Rabe, K., Ayres-Silva, J., Tschumper, R., Dyke, D.V., Slager, S., Fonseca, R., Shanafelt, T., Kay, N. & Braggio, E. (2014) Monoclonal B-cell lymphocytosis is characterized by mutations in CLL putative driver genes and clonal heterogeneity many years before disease progression. Leukemia, DOI: 10.1038/leu.2014.226 [Epub ahead of print].
74. Oscier, D.G., Rose-Zerilli, M.J.J., Winkelmann, N., Gonzalez de Castro, D., Gomez, B., Forster, J., Parker, H., Parker, A., Gardiner, A., Collins, A., Else, M., Cross, N.C.P., Catovsky, D. & Strefford, J.C. (2013) The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood, 120, 4441-4443.
75. Ouillette, P., Erba, H., Kujawski, L., Kaminski, M., Shedden, K. & Malek, S.N. (2008) Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Research, 68, 1012-1021.
76. Ouillette, P., Fossum, S., Parkin, B., Ding, L., Bockenstedt, P., Al-Zoubi, A., Shedden, K. & Malek, S.N. (2010) Aggressive chronic lymphocytic leukemia with elevated genomic complexity is associated with multiple gene defects in the response to DNA double-strand breaks. Clinical Cancer Research, 16, 835-847.
77. Ouillette, P., Collins, R., Shakhan, S., Li, J., Li, C., Shedden, K. & Malek, S.N. (2011a) The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia. Clinical Cancer Research, 17, 6778-6790.
78. Ouillette, P., Collins, R., Shakhan, S., Li, J., Peres, E., Kujawski, L., Talpaz, M., Kaminski, M., Li, C., Shedden, K. & Malek, S.N. (2011b) Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia. Blood, 118, 3051-3061.
79. Ouillette, P., Saiya-Cork, K., Seymour, E., Li, C., Shedden, K. & Malek, S.N. (2013) Clonal evolution, genomic drivers, and effects of therapy in chronic lymphocytic leukemia. Clinical Cancer Research, 19, 2893-2904.
80. Parikh, S.A., Rabe, K.G., Call, T.G., Zent, C.S., Habermann, T.M., Ding, W., Leis, J.F., Schwager, S.M., Hanson, C.A., Macon, W.R., Kay, N.E., Slager, S.L. & Shanafelt, T.D. (2013) Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients. British Journal of Haematology, 162, 774-782.
81. Parker, H., Rose-Zerilli, M., Parker, A., Chaplin, T., Chen, X., Wade, R., Gardiner, A., Griffiths, M., Collins, A., Young, B.D., Oscier, D.G. & Strefford, J.C. (2011) 13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia. Leukemia, 25, 489-497.
82. Pettitt, A.R., Jackson, R., Carruthers, S., Dodd, J., Dodd, S., Oates, M., Johnson, G.G., Schuh, A., Matutes, E., Dearden, C.E., Catovsky, D., Radford, J.A., Bloor, A., Follows, G.A., Devereux, S., Kruger, A., Blundell, J., Agrawal, S., Allsup, D., Proctor, S., Heartin, E., Oscier, D., Hamblin, T.J., Rawstron, A. & Hillmen, P. (2012) Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial. Journal of Clinical Oncology, 30, 1647-1655.
83. Pfeifer, D., Pantic, M., Skatulla, I., Rawluk, J., Kreutz, C., Martens, U.M., Fisch, P., Timmer, J. & Veelken, H. (2007) Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood, 109, 1202-1210.
84. Poncet, D., Belleville, A., t'kint de Roodenbeke, C., Roborel de Climens, A., Ben Simon, E., Merle-Beral, H., Callet-Bauchu, E., Salles, G., Sabatier, L., Delic, J. & Gilson, E. (2007) Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia. Blood, 111, 2388-2391.
85. Puente, X.S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G.R., Villamor, N., Escaramis, G., Jares, P., Beà, S., González-Díaz, M., Bassaganyas, L., Baumann, T., Juan, M., López-Guerra, M., Colomer, D., Tubío, J.M., López, C., Navarro, A., Tornador, C., Aymerich, M., Rozman, M., Hernández, J.M., Puente, D.A., Freije, J.M., Velasco, G., Gutiérrez-Fernández, A., Costa, D., Carrió, A., Guijarro, S., Enjuanes, A., Hernández, L., Yagüe, J., Nicolás, P., Romeo-Casabona, C.M., Himmelbauer, H., Castillo, E., Dohm, J.C., de Sanjosé, S., Piris, M.A., de Alava, E., Miguel, J.S., Royo, R., Gelpí, J.L., Torrents, D., Orozco, M., Pisano, D.G., Valencia, A., Guigó, R., Bayés, M., Heath, S., Gut, M., Klatt, P., Marshall, J., Raine, K., Stebbings, L.A., Futreal, P.A., Stratton, M.R., Campbell, P.J., Gut, I., López-Guillermo, A., Estivill, X., Montserrat, E., López-Otín, C. & Campo, E. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature, 475, 101-105.
86. Quesada, V., Conde, L., Villamor, N., Ordóñez, G.R., Jares, P., Bassaganyas, L., Ramsay, A.J., Beà, S., Pinyol, M., Martínez-Trillos, A., López-Guerra, M., Colomer, D., Navarro, A., Baumann, T., Aymerich, M., Rozman, M., Delgado, J., Giné, E., Hernández, J.M., González-Díaz, M., Puente, D.A., Velasco, G., Freije, J.M., Tubío, J.M., Royo, R., Gelpí, J.L., Orozco, M., Pisano, D.G., Zamora, J., Vázquez, M., Valencia, A., Himmelbauer, H., Bayés, M., Heath, S., Gut, M., Gut, I., Estivill, X., López-Guillermo, A., Puente, X.S., Campo, E. & López-Otín, C. (2011) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nature Genetics, 44, 47-52.
87. Raghavan, M., Lillington, D.M., Skoulakis, S., Debernardi, S., Chaplin, T., Foot, N.J., Lister, T.A. & Young, B.D. (2005) Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias. Cancer Research, 65, 375-378.
88. Rai, K.R., Sawitsky, A., Cronkite, E.P., Chanana, A.D., Levy, R.N. & Pasternack, B.S. (1975) Clinical staging of chronic lymphocytic leukemia. Blood, 46, 219-234.
89. Ramsay, A.J., Quesada, V., Foronda, M., Conde, L., Martínez-Trillos, A., Villamor, N., Rodríguez, D., Kwarciak, A., Garabaya, C., Gallardo, M., López-Guerra, M., López-Guillermo, A., Puente, X.S., Blasco, M.A., Campo, E. & López-Otín, C. (2013) POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia. Nature Genetics, 45, 526-530.
90. Rasi, S., Monti, S., Spina, V., Foa', R., Gaidano, G. & Rossi, D. (2001) Analysis of NOTCH1 mutations in monoclonal B cell lymphocytosis. Haematologica, 97, 153-154.
91. Rausch, T., Jones, D.T., Zapatka, M., Stütz, A.M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P.A., Pfaff, E., Tica, J., Wang, Q., Massimi, L., Witt, H., Bender, S., Pleier, S., Cin, H., Hawkins, C., Beck, C., von Deimling, A., Hans, V., Brors, B., Eils, R., Scheurlen, W., Blake, J., Benes, V., Kulozik, A.E., Witt, O., Martin, D., Zhang, C., Porat, R., Merino, D.M., Wasserman, J., Jabado, N., Fontebasso, A., Bullinger, L., Rücker, F.G., Döhner, K., Döhner, H., Koster, J., Molenaar, J.J., Versteeg, R., Kool, M., Tabori, U., Malkin, D., Korshunov, A., Taylor, M.D., Lichter, P., Pfister, S.M. & Korbel, J.O. (2012) Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell, 148, 59-71.
92. Rawstron, A.C., Bennett, F.L., O'Connor, S.J., Kwok, M., Fenton, J.A., Plummer, M., de Tute, R., Owen, R.G., Richards, S.J., Jack, A.S. & Hillmen, P. (2008) Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. New England Journal of Medicine, 359, 575-583.
93. Riches, J.C., O'Donovan, C.J., Kingdon, S.J., McClanahan, F., Clear, A.J., Neuberg, D.S., Werner, L., Croce, C.M., Ramsay, A.G., Rassenti, L.Z., Kipps, T.J. & Gribben, J.G. (2014) Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations. Blood, 123, 4101-4110.
94. Rodríguez, D., Ramsay, A.J., Quesada, V., Garabaya, C., Campo, E., Freije, J.M. & López-Otín, C. (2013) Functional analysis of sucrase-isomaltase mutations from chronic lymphocytic leukemia patients. Human Molecular Genetics, 22, 2273-2282.
95. Roos, G., Kröber, A., Grabowski, P., Kienle, D., Bühler, A., Döhner, H., Rosenquist, R. & Stilgenbauer, S. (2008) Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood, 111, 2246-2252.
96. Rosati, E., Sabatini, R., Rampino, G., Tabilio, A., Di Ianni, M., Fettucciari, K., Bartoli, A., Coaccioli, S., Screpanti, I. & Marconi, P. (2009) Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood, 113, 856-865.
97. Rosati, E., Sabatini, R., De Falco, F., Papa, B.D., Falzetti, F., Di Ianni, M., Cavalli, L., Fettucciari, K., Bartoli, A., Screpanti, I. & Marconi, P. (2013) γ-Secretase inhibitor I induces apoptosis in chronic lymphocytic leukemia cells by proteasome inhibition, endoplasmic reticulum stress increase and Notch down-regulation. International Journal of Cancer, 132, 1940-1953.
98. Rose-Zerilli, M., Forster, J., Parker, H., Parker, A., Rodriguez, A., Chaplin, T., Gardiner, A., Steele, A.J., Collins, A., Young, B.D., Skowronska, A., Catovsky, D., Stankovic, T., Oscier, D.G. & Strefford, J.C. (2014) ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia, data from the UK LRF CLL4 trial. Haematologica, 99, 736-742.
99. Rossi, D., Cerri, M., Deambrogi, C., Sozzi, E., Cresta, S., Rasi, S., De Paoli, L., Spina, V., Gattei, V., Capello, D., Forconi, F., Lauria, F. & Gaidano, G. (2009a) The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clinical Cancer Research, 15, 995-1004.
100. Rossi, D., Lobetti Bodoni, C., Genuardi, E., Monitillo, L., Drandi, D., Cerri, M., Deambrogi, C., Ricca, I., Rocci, A., Ferrero, S., Bernocco, E., Capello, D., De Paoli, L., Bergui, L., Boi, M., Omedè, P., Massaia, M., Tarella, C., Passera, R., Boccadoro, M., Gaidano, G. & Ladetto, M. (2009b) Telomere length is an independent predictor of survival, treatment requirement and Richter's syndrome transformation in chronic lymphocytic leukemia. Leukemia, 23, 1062-1072.
101. Rossi, D., Deaglio, S., Dominguez-Sola, D., Rasi, S., Vaisitti, T., Agostinelli, C., Spina, V., Bruscaggin, A., Monti, S., Cerri, M., Cresta, S., Fangazio, M., Arcaini, L., Lucioni, M., Marasca, R., Thieblemont, C., Capello, D., Facchetti, F., Kwee, I., Pileri, S.A., Foà, R., Bertoni, F., Dalla-Favera, R., Pasqualucci, L. & Gaidano, G. (2011a) Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma. Blood, 118, 4930-4934.
102. Rossi, D., Rasi, S., Fabbri, G., Spina, V., Fangazio, M., Forconi, F., Marasca, R., Laurenti, L., Bruscaggin, A., Cerri, M., Monti, S., Cresta, S., Famà, R., De Paoli, L., Bulian, P., Gattei, V., Guarini, A., Deaglio, S., Capello, D., Rabadan, R., Pasqualucci, L., Dalla-Favera, R., Foà, R. & Gaidano, G. (2011b) Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood, 119, 521-529.
103. Rossi, D., Bruscaggin, A., Spina, V., Rasi, S., Khiabanian, H., Messina, M., Fangazio, M., Vaisitti, T., Monti, S., Chiaretti, S., Guarini, A., Del Giudice, I., Cerri, M., Cresta, S., Deambrogi, C., Gargiulo, E., Gattei, V., Forconi, F., Bertoni, F., Deaglio, S., Rabadan, R., Pasqualucci, L., Foà, R., Dalla-Favera, R. & Gaidano, G. (2011c) Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood, 118, 6904-6908.
104. Rossi, D., Rasi, S., Spina, V., Fangazio, M., Monti, S., Greco, M., Ciardullo, C., Famà, R., Cresta, S., Bruscaggin, A., Laurenti, L., Martini, M., Musto, P., Forconi, F., Marasca, R., Larocca, L.M., Foà, R. & Gaidano, G. (2012) Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. British Journal of Haematology, 158, 426-429.
105. Rossi, D., Spina, V., Bomben, R., Rasi, S., Dal-Bo, M., Bruscaggin, A., Rossi, F.M., Monti, S., Degan, M., Ciardullo, C., Serra, R., Zucchetto, A., Nomdedeu, J., Bulian, P., Grossi, A., Zaja, F., Pozzato, G., Laurenti, L., Efremov, D.G., Di-Raimondo, F., Marasca, R., Forconi, F., Del Poeta, G., Gaidano, G. & Gattei, V. (2013a) Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood, 121, 4902-4905.
106. Rossi, D., Rasi, S., Spina, V., Bruscaggin, A., Monti, S., Ciardullo, C., Deambrogi, C., Khiabanian, H., Serra, R., Bertoni, F., Forconi, F., Laurenti, L., Marasca, R., Dal-Bo, M., Rossi, F.M., Bulian, P., Nomdedeu, J., Del Poeta, G., Gattei, V., Pasqualucci, L., Rabadan, R., Foà, R., Dalla-Favera, R. & Gaidano, G. (2013b) Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood, 121, 1403-1412.
107. Rossi, D., Khiabanian, H., Spina, V., Ciardullo, C., Bruscaggin, A., Famà, R., Rasi, S., Monti, S., Deambrogi, C., De Paoli, L., Wang, J., Gattei, V., Guarini, A., Foà, R., Rabadan, R. & Gaidano, G. (2014) Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood, 123, 2139-2147.
108. Schnaiter, A., Paschka, P., Rossi, M., Zenz, T., Bühler, A., Winkler, D., Cazzola, M., Döhner, K., Edelmann, J., Mertens, D., Kless, S., Mack, S., Busch, R., Hallek, M., Döhner, H. & Stilgenbauer, S. (2013) NOTCH1, SF3B1, and TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results from the CLL2H trial of the GCLLSG. Blood, 122, 1266-1270.
109. Schuh, A., Becq, J., Humphray, S., Alexa, A., Burns, A., Clifford, R., Feller, S.M., Grocock, R., Henderson, S., Khrebtukova, I., Kingsbury, Z., Luo, S., McBride, D., Murray, L., Menju, T., Timbs, A., Ross, M., Taylor, J. & Bentley, D. (2012) Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns. Blood, 120, 4191-4196.
110. Schwaenen, C., Nessling, M., Wessendorf, S., Salvi, T., Wrobel, G., Radlwimmer, B., Kestler, H.A., Haslinger, C., Stilgenbauer, S., Dohner, H., Bentz, M. & Lichter, P. (2004) Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations. Proceedings of the National Academy of Sciences of the United States of America, 101, 1039-1044.
111. Sellmann, L., Gesk, S., Walter, C., Ritgen, M., Harder, L., Martín-Subero, J.I., Schroers, R., Siemer, D., Nückel, H., Dyer, M.J., Dührsen, U., Siebert, R., Dürig, J. & Küppers, R. (2007) Trisomy 19 is associated with trisomy 12 and mutated IGHV genes in B-chronic lymphocytic leukaemia. British Journal of Haematology, 138, 217-220.
112. Seymour, J.F., Davids, M.S., Pagel, J.M., Kahl, B.S., Wierda, W.G., Miller, T.P., Gerecitano, J.F., Kipps, T.J., Anderson, M.A., Huang, D.C., Rudersdorf, N.K., Gressick, L.A., Montalvo, B.P., Yang, J., Busman, T.A., Dunbar, M., Cerri, E., Enschede, S.H., Humerickhouse, R.A. & Roberts, A.W. (2013) Bcl-2 Inhibitor ABT-199 (GDC-0199) monotherapy shows anti-tumor activity including complete remissions in high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Blood, 122, 872.
113. Shedden, K., Li, Y., Ouillette, P. & Malek, S.N. (2012) Characteristics of chronic lymphocytic leukemia with somatically acquired mutations in NOTCH1 exon 34. Leukemia, 26, 1108-1110.
114. Souers, A.J., Leverson, J.D., Boghaert, E.R., Ackler, S.L., Catron, N.D., Chen, J., Dayton, B.D., Ding, H., Enschede, S.H., Fairbrother, W.J., Huang, D.C., Hymowitz, S.G., Jin, S., Khaw, S.L., Kovar, P.J., Lam, L.T., Lee, J., Maecker, H.L., Marsh, K.C., Mason, K.D., Mitten, M.J., Nimmer, P.M., Oleksijew, A., Park, C.H., Park, C.M., Phillips, D.C., Roberts, A.W., Sampath, D., Seymour, J.F., Smith, M.L., Sullivan, G.M., Tahir, S.K., Tse, C., Wendt, M.D., Xiao, Y., Xue, J.C., Zhang, H., Humerickhouse, R.A., Rosenberg, S.H. & Elmore, S.W. (2013) ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nature Medicine, 19, 202-208.
115. Speedy, H.E., Di Bernardo, M.C., Sava, G.P., Dyer, M.J., Holroyd, A., Wang, Y., Sunter, N.J., Mansouri, L., Juliusson, G., Smedby, K.E., Roos, G., Jayne, S., Majid, A., Dearden, C., Hall, A.G., Mainou-Fowler, T., Jackson, G.H., Summerfield, G., Harris, R.J., Pettitt, A.R., Allsup, D.J., Bailey, J.R., Pratt, G., Pepper, C., Fegan, C., Rosenquist, R., Catovsky, D., Allan, J.M. & Houlston, R.S. (2014) A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nature Genetics, 46, 56-60.
116. Stankovic, T., Weber, P., Stewart, G., Bedenham, T., Murray, J., Byrd, P.J., Moss, P.A. & Taylor, A.M. (1999) Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia. Lancet, 353, 26-29.
117. Stephens, P.J., Greenman, C.D., Fu, B., Yang, F., Bignell, G.R., Mudie, L.J., Pleasance, E.D., Lau, K.W., Beare, D., Stebbings, L.A., McLaren, S., Lin, M.L., McBride, D.J., Varela, I., Nik-Zainal, S., Leroy, C., Jia, M., Menzies, A., Butler, A.P., Teague, J.W., Quail, M.A., Burton, J., Swerdlow, H., Carter, N.P., Morsberger, L.A., Iacobuzio-Donahue, C., Follows, G.A., Green, A.R., Flanagan, A.M., Stratton, M.R., Futreal, P.A. & Campbell, P.J. (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell, 144, 27-40.
118. Stilgenbauer, S., Bullinger, L., Benner, A., Wildenberger, K., Bentz, M., Döhner, K., Ho, A.D., Lichter, P. & Döhner, H. (1999) Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia. Leukemia, 13, 1331-1334.
119. Stilgenbauer, S., Schnaiter, A., Paschka, P., Zenz, T., Rossi, M., Döhner, K., Bühler, A., Böttcher, S., Ritgen, M., Kneba, M., Winkler, D., Tausch, E., Hoth, P., Edelmann, J., Mertens, D., Bullinger, L., Bergmann, M., Kless, S., Mack, S., Jäger, U., Patten, N., Wu, L., Wenger, M.K., Fingerle-Rowson, G., Lichter, P., Cazzola, M., Wendtner, C.M., Fink, A.M., Fischer, K., Busch, R., Hallek, M. & Döhner, H. (2014) Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood, 123, 3247-3254.
120. Strefford, J.C., Sutton, L.A., Baliakas, P., Agathangelidis, A., Malčíková, J., Plevova, K., Scarfó, L., Davis, Z., Stalika, E., Cortese, D., Cahill, N., Pedersen, L.B., di Celle, P.F., Tzenou, T., Geisler, C., Panagiotidis, P., Langerak, A.W., Chiorazzi, N., Pospisilova, S., Oscier, D., Davi, F., Belessi, C., Mansouri, L., Ghia, P., Stamatopoulos, K. & Rosenquist, R. (2013) Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2. Leukemia, 27, 2196-2199.
121. Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J. & Vardiman, J.W. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition. World Health Organization, Lyon, France.
122. Tam, C.S., Otero-Palacios, J., Abruzzo, L.V., Jorgensen, J.L., Ferrajoli, A., Wierda, W.G., Lerner, S., O'Brien, S. & Keating, M.J. (2008) Chronic lymphocytic leukaemia CD20 expression is dependent on the genetic subtype: a study of quantitative flow cytometry and fluorescent in-situ hybridization in 510 patients. British Journal of Haematology, 141, 36-40.
123. Tsimberidou, A.M., O'Brien, S., Khouri, I., Giles, F.J., Kantarjian, H.M., Champlin, R., Wen, S., Do, K.A., Smith, S.C., Lerner, S., Freireich, E.J. & Keating, M.J. (2006) Clinical outcomes and prognostic factors in patients with Richter's syndrome treated with chemotherapy or chemoimmunotherapy with or without stem-cell transplantation. Journal of Clinical Oncology, 24, 2343-2351.
124. Villamor, N., Conde, L., Martínez-Trillos, A., Cazorla, M., Navarro, A., Beà, S., López, C., Colomer, D., Pinyol, M., Aymerich, M., Rozman, M., Abrisqueta, P., Baumann, T., Delgado, J., Giné, E., González-Díaz, M., Hernández, J.M., Colado, E., Payer, A.R., Rayon, C., Navarro, B., José Terol, M., Bosch, F., Quesada, V., Puente, X.S., López-Otín, C., Jares, P., Pereira, A., Campo, E. & López-Guillermo, A. (2013) NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia, 27, 1100-1106.
125. Wang, L., Lawrence, M.S., Wan, Y., Stojanov, P., Sougnez, C., Stevenson, K., Werner, L., Sivachenko, A., DeLuca, D.S., Zhang, L., Vartanov, A., Fernandes, S.M., Goldstein, N.R., Folco, E.G., Cibilskis, K., Tesar, B., Sievers, Q.L., Shefler, E., Gabriel, S., Hacohen, N., Reed, R., Meyerson, M., Golub, T.R., Lander, E.S., Neuberg, D., Brown, J.R., Getz, G. & Wu, C.J. (2011) SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. New England Journal of Medicine, 365, 2497-2506.
126. Wiestner, A. (2013) Targeting B-cell receptor signaling for anticancer therapy: the bruton's tyrosine kinase inhibitor ibrutinib induces impressive responses in B-cell malignancies. Journal of Clinical Oncology, 31, 128-130.
127. Woyach, J.A., Furman, R.R., Liu, T.M., Oze, H.G., Zapatka, M., Rupper, A.S., Xue, L., Li, D., Steggerda, S.M., Versele, M.D., Sandeeo, S., Zhang, J., Yilmaz, A.S., Jaglowski, S., Blum, K.A., Lozanski, A., Lozanski, G.J., Danelle, F., Barrientos, J., Lichter, P., Stilgenbauer, S., Buggy, J.J., Chang, B.Y., Johnson, A. & Byrd, J.C. (2014) Resistance mechanisms for the bruton's tyrosine kinase inhibitor ibrutinib. The New England Journal of Medicine, 370, 2286-2294.
128. Zenz, T., Kröber, A., Scherer, K., Häbe, S., Bühler, A., Benner, A., Denzel, T., Winkler, D., Edelmann, J., Schwänen, C., Döhner, H. & Stilgenbauer, S. (2008) Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood, 112, 3322-3329.
129. Zenz, T., Vollmer, D., Trbusek, M., Smardova, J., Benner, A., Soussi, T., Helfrich, H., Heuberger, M., Hoth, P., Fuge, M., Denzel, T., Häbe, S., Malcikova, J., Kuglik, P., Truong, S., Patten, N., Wu, L., Oscier, D., Ibbotson, R., Gardiner, A., Tracy, I., Lin, K., Pettitt, A., Pospisilova, S., Mayer, J., Hallek, M., Döhner, H., Stilgenbauer, S. & European Research Initiative on CLL (ERIC) (2010) TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia, 24, 2072-2079.
130. Zhang, X., Reis, M., Khoriaty, R., Li, Y., Ouillette, P., Samayoa, J., Carter, H., Karchin, R., Li, M., Diaz, L.A.J., Velculescu, V.E., Papadopoulos, N., Kinzler, K.W., Vogelstein, B. & Malek, S.N. (2011) Sequence analysis of 515 kinase genes in chronic lymphocytic leukemia. Leukemia, 25, 1908-1910.
131. Zucchetto, A., Caldana, C., Benedetti, D., Tissino, E., Rossi, F.M., Hutterer, E., Pozzo, F., Bomben, R., Dal Bo, M., D'Arena, G., Zaja, F., Pozzato, G., Di Raimondo, F., Hartmann, T.N., Rossi, D., Gaidano, G., Del Poeta, G. & Gattei, V. (2013) CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism. Blood, 122, 3317-3321.