期刊论文详细信息
BMC Medicine
The genomic landscape of chronic lymphocytic leukemia: clinical implications
Carlos López-Otín1  Elías Campo2  Xose S Puente1  David Rodríguez1  Andrew J Ramsay1  Víctor Quesada1 
[1] Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo - IUOPA, Oviedo, Spain;Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Universitat de Barcelona, IDIBAPS, Barcelona, Spain
关键词: Personalized medicine;    Driver mutations;    Epigenomics;    Genomics;    Chronic lymphocytic leukemia;   
Others  :  857037
DOI  :  10.1186/1741-7015-11-124
 received in 2013-02-08, accepted in 2013-04-12,  发布年份 2013
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【 摘 要 】

A precise understanding of the genomic and epigenomic features of chronic lymphocytic leukemia (CLL) may benefit the study of the disease’s staging and treatment. While recent reports have shed some light on these aspects, several challenges need to be addressed before translating this research into clinical practice. Thus, even the best candidate driver genes display low mutational rates compared to other tumors. This means that a large percentage of cases do not display clear tumor-driving point mutations, or show candidate driving point mutations with no obvious biochemical relationship to the more frequently mutated genes. This genomic landscape probably reflects either an unknown underlying biochemical mechanism playing a key role in CLL or multiple biochemical pathways independently driving the development of this tumor. The elucidation of either scenario will have important consequences on the clinical management of CLL. Herein, we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterize the underlying biochemical events that drive this disease.

【 授权许可】

   
2013 Quesada et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S: From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 2010, 10:37-50.
  • [2]Gaidano G, Foa R, Dalla-Favera R: Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest 2012, 122:3432-3438.
  • [3]Klein U, Dalla-Favera R: Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol 2008, 8:22-33.
  • [4]Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK: Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999, 94:1848-1854.
  • [5]Zenz T, Kröber A, Scherer K, Häbe S, Buhler A, Benner A, Denzel T, Winkler D, Edelmann J, Schwänen C, Döhner H, Stilgenbauer S: Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood 2008, 112:3322-3329.
  • [6]Austen B, Powell JE, Alvi A, Edwards I, Hooper L, Starczynski J, Taylor AM, Fegan C, Moss P, Stankovic T: Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood 2005, 106:3175-3182.
  • [7]Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M, Marce S, Lopez-Guillermo A, Campo E, Montserrat E: ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003, 348:1764-1775.
  • [8]Damle RN, Temburni S, Calissano C, Yancopoulos S, Banapour T, Sison C, Allen SL, Rai KR, Chiorazzi N: CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells. Blood 2007, 110:3352-3359.
  • [9]Ouillette P, Collins R, Shakhan S, Li J, Peres E, Kujawski L, Talpaz M, Kaminski M, Li C, Shedden K, Malek SN: Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia. Blood 2011, 118:3051-3061.
  • [10]Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM: Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2002, 99:15524-15529.
  • [11]Klein U, Lia M, Crespo M, Siegel R, Shen Q, Mo T, Ambesi-Impiombato A, Califano A, Migliazza A, Bhagat G, Dalla-Favera R: The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 2010, 17:28-40.
  • [12]Metzker ML: Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46.
  • [13]Stratton MR, Campbell PJ, Futreal PA: The cancer genome. Nature 2009, 458:719-724.
  • [14]Meyerson M, Gabriel S, Getz G: Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 2010, 11:685-696.
  • [15]Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C, Downey SL, Johnson BE, Fouse SD, Delaney A, Zhao Y, Olshen A, Ballinger T, Zhou X, Forsberg KJ, Gu J, Echipare L, O'Geen H, Lister R, Pelizzola M, Xi Y, Epstein CB, Bernstein BE, Hawkins RD, Ren B, Chung WY, Gu H, Bock C, Gnirke A, Zhang MQ, Haussler D: Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nat Biotechnol 2010, 28:1097-1105.
  • [16]Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D: Patterns of somatic mutation in human cancer genomes. Nature 2007, 446:153-158.
  • [17]Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabe RR, Bhan MK, Calvo F, Eerola I, Gerhard DS, Guttmacher A, Guyer M, Hemsley FM, Jennings JL, Kerr D, Klatt P, Kolar P, Kusada J, Lane DP, Laplace F, Youyong L, Nettekoven G, Ozenberger B, Peterson J, Rao TS, Remacle J, Schafer AJ, Shibata T, Stratton MR, Vockley JG, International Cancer Genome Consortium: International network of cancer genome projects. Nature 2010, 464:993-998.
  • [18]Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N, Escaramis G, Jares P, Bea S, Gonzalez-Diaz M, Bassaganyas L, Baumann T, Juan M, López-Guerra M, Colomer D, Tubío JM, López C, Navarro A, Tornador C, Aymerich M, Rozman M, Hernández JM, Puente DA, Freije JM, Velasco G, Gutiérrez-Fernández A, Costa D, Carrió A, Guijarro S, Enjuanes A: Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011, 475:101-105.
  • [19]Sportoletti P, Baldoni S, Cavalli L, Del Papa B, Bonifacio E, Ciurnelli R, Bell AS, Di Tommaso A, Rosati E, Crescenzi B, Mecucci C, Screpanti I, Marconi P, Martelli MF, Di Ianni M, Falzetti F: NOTCH1 PEST domain mutation is an adverse prognostic factor in B-CLL. Br J Haematol 2010, 151:404-406.
  • [20]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 LM, Marasca R, Gattei V, Oscier D, Bertoni F, Mullighan CG, Foá R, Pasqualucci L, Rabadan R, Dalla-Favera R, Gaidano G: Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med 2011, 208:1389-1401.
  • [21]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: Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 2012, 119:521-529.
  • [22]Villamor N, Conde L, Martinez-Trillos A, Cazorla M, Navarro A, Bea S, Lopez C, Colomer D, Pinyol M, Aymerich M, Rozman M, Abrisqueta P, Baumann T, Delgado J, Giné E, González-Díaz M, Hernández JM, Colado E, Payer AR, Rayon C, Navarro B, José Terol M, Bosch F, Quesada V, Puente XS, López-Otín C, Jares P, Pereira A, Campo E, López-Guillermo A: NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia 2012.
  • [23]Rosati E, Sabatini R, De Falco F, Del Papa B, Falzetti F, Di Ianni M, Cavalli L, Fettucciari K, Bartoli A, Screpanti I, Marconi P: gamma-Secretase inhibitor I induces apoptosis in chronic lymphocytic leukemia cells by proteasome inhibition, endoplasmic reticulum stress increase and notch down-regulation. Int J Cancer 2012, 132:1940-1953.
  • [24]Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L, Ramsay AJ, Bea S, Pinyol M, Martinez-Trillos A, López-Guerra M, Colomer D, Navarro A, Baumann T, Aymerich M, Rozman M, Delgado J, Giné E, Hernández JM, González-Díaz M, Puente DA, Velasco G, Freije JM, Tubío JM, Royo R, Gelpí JL, Orozco M, Pisano DG, Zamora J, Vázquez M: Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2011, 44:47-52.
  • [25]Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L, Zhang W, Vartanov AR, Fernandes SM, Goldstein NR, Folco EG, Cibulskis K, Tesar B, Sievers QL, Shefler E, Gabriel S, Hacohen N, Reed R, Meyerson M, Golub TR, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ: SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011, 365:2497-2506.
  • [26]Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, Ishigami K, Watanabe H, Kitahara T, Yoshida T, Nakajima H, Tani T, Horinouchi S, Yoshida M: Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 2007, 3:576-583.
  • [27]Corrionero A, Minana B, Valcarcel J: Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev 2011, 25:445-459.
  • [28]Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H: Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011, 478:64-69.
  • [29]Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, Pellagatti A, Wainscoat JS, Hellstrom-Lindberg E, Gambacorti-Passerini C, Godfrey AL, Rapado I, Cvejic A, Rance R, McGee C, Ellis P, Mudie LJ, Stephens PJ, McLaren S, Massie CE, Tarpey PS, Varela I, Nik-Zainal S, Davies HR, Shlien A, Jones D, Raine K, Hinton J, Butler AP, Teague JW: Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011, 365:1384-1395.
  • [30]Makishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A, Przychodzen B, Bupathi M, Guinta K, Afable MG, Sekeres MA, Padgett RA, Tiu RV, Maciejewski JP: Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood 2012, 119:3203-3210.
  • [31]Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, Miller DK, Wilson PJ, Patch AM, Wu J, Chang DK, Cowley MJ, Gardiner BB, Song S, Harliwong I, Idrisoglu S, Nourse C, Nourbakhsh E, Manning S, Wani S, Gongora M, Pajic M, Scarlett CJ, Gill AJ, Pinho AV, Rooman I, Anderson M, Holmes O, Leonard C, Taylor D: Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012, 491:399-405.
  • [32]Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM: Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 2013, 45:133-135.
  • [33]Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G: Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 2012, 486:353-360.
  • [34]Ramsay AJ, Rodriguez D, Villamor N, Kwarciak A, Tejedor JR, Valcarcel J, Lopez-Guillermo A, Martinez-Trillos A, Puente XS, Campo E, López-Otín C, Quesada V: Frequent somatic mutations in components of the RNA processing machinery in chronic lymphocytic leukemia. Leukemia 2012.
  • [35]Visconte V, Makishima H, Maciejewski JP, Tiu RV: Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders. Leukemia 2012, 26:2447-2454.
  • [36]Isono K, Mizutani-Koseki Y, Komori T, Schmidt-Zachmann MS, Koseki H: Mammalian polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1. Genes Dev 2005, 19:536-541.
  • [37]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: Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 2011, 118:6904-6908.
  • [38]Ramsay AJ, Martinez-Trillos A, Jares P, Rodriguez D, Kwarciak A, Quesada V: Next-generation sequencing reveals the secrets of the chronic lymphocytic leukemia genome. Clin Transl Oncol 2013, 15:3-8.
  • [39]Rossi D, Fangazio M, Rasi S, Vaisitti T, Monti S, Cresta S, Chiaretti S, Del Giudice I, Fabbri G, Bruscaggin A, Spina V, Deambrogi C, Marinelli M, Famà R, Greco M, Daniele G, Forconi F, Gattei V, Bertoni F, Deaglio S, Pasqualucci L, Guarini A, Dalla-Favera R, Foà R, Gaidano G: Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood 2012, 119:2854-2862.
  • [40]Gonzalez D, Martinez P, Wade R, Hockley S, Oscier D, Matutes E, Dearden CE, Richards SM, Catovsky D, Morgan GJ: 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. J Clin Oncol 2011, 29:2223-2229.
  • [41]Mori J, Takahashi Y, Tanimoto T: SF3B1 in chronic lymphocytic leukemia. N Engl J Med 2012, 366:1057. author reply 10571058
  • [42]Quesada V, Ramsay AJ, Lopez-Otin C: Chronic lymphocytic leukemia with SF3B1 mutation. N Engl J Med 2012, 366:2530.
  • [43]Kulis M, Heath S, Bibikova M, Queiros AC, Navarro A, Clot G, Martinez-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 JL: Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nat Genet 2012, 44:1236-1242.
  • [44]Ding L, Wendl MC, Koboldt DC, Mardis ER: Analysis of next-generation genomic data in cancer: accomplishments and challenges. Hum Mol Genet 2010, 19:R188-196.
  • [45]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 FM, Bulian P, Nomdedeu J, Del Poeta G, Gattei V, Pasqualucci L, Rabadan R, Foà R, Dalla-Favera R, Gaidano G: Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood 2013, 121:1403-1412.
  • [46]Schwaederlé M, Ghia E, Rassenti L, Obara M, Dell'aquila ML, Fecteau-Farah J, Kipps TJ: Subclonal evolution involving SF3B1 mutations in chronic lymphocytic leukemia. Leukemia 2013.
  • [47]Rossi D, Spina V, Forconi F, Capello D, Fangazio M, Rasi S, Martini M, Gattei V, Ramponi A, Larocca LM, Bertoni F, Gaidano G: Molecular history of Richter syndrome: origin from a cell already present at the time of chronic lymphocytic leukemia diagnosis. Int J Cancer 2012, 130:3006-3010.
  • [48]Landau D-A, Carter S, Stojanov P, Stevenson KE, Mckenna A, Lawrence M, Sougnez C, Sivachenko A, Wang L, Zhang W, Sachet S, Vartanov AR, Fernandes SM, Cibulskis K, Tesar B, Gabriel S, Meyerson M, Lander ES, Neuberg DS, Brown JR, Getz G, Wu CJ: The evolution and impact of subclonal mutations in chronic lymphocytic leukemia. In 54th ASH Annual Meeting and Exposition: December 8-11, 2012. Atlanta, GA; 2012. abstract 5
  • [49]Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, Sougnez C, Stewart C, Sivachenko A, Wang L, Wan Y, Zhang W, Shukla SA, Vartanov A, Fernandes SM, Saksena G, Cibulskis K, Tesar B, Gabriel S, Hacohen N, Meyerson M, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ: Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 2013, 152:714-726.
  • [50]Puente XS, Lopez-Otin C: The evolutionary biography of chronic lymphocytic leukemia. Nat Genet 2013, 45:229-231.
  • [51]Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, Pucciarini A, Bigerna B, Pacini R, Wells VA, Sportoletti P, Pettirossi V, Mannucci R, Elliott O, Liso A, Ambrosetti A, Pulsoni A, Forconi F, Trentin L, Semenzato G, Inghirami G, Capponi M, Di Raimondo F, Patti C, Arcaini L, Musto P, Pileri S, Haferlach C, Schnittger S, Pizzolo G: BRAF mutations in hairy-cell leukemia. N Engl J Med 2011, 364:2305-2315.
  • [52]Reva B, Antipin Y, Sander C: Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res 2011, 39:e118.
  • [53]Gonzalez-Perez A, Lopez-Bigas N: Functional impact bias reveals cancer drivers. Nucleic Acids Res 2012, 40:e169.
  • [54]Nehrt NL, Peterson TA, Park D, Kann MG: Domain landscapes of somatic mutations in cancer. BMC Genomics 2012, 13:S9.
  • [55]Rozovski U, Keating M, Estrov Z: The significance of spliceosome mutations in chronic lymphocytic leukemia. Leuk Lymphoma 2013. [Epub ahead of print.]
  • [56]Ramsay AJ, Quesada V, Foronda M, Conde L, Martinez-Trillos A, Villamor N, Rodriguez D, Kwarciak A, Garabaya C, Gallardo M, López-Guerra M, López-Guillermo A, Puente XS, Blasco MA, Campo E, López-Otín C: POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia. Nat Genet 2013, 45:526-530.
  • [57]Rodriguez D, Ramsay AJ, Quesada V, Garabaya C, Campo E, Freije JM, Lopez-Otin C: Functional analysis of sucrase-isomaltase mutations from chronic lymphocytic leukemia patients. Hum Mol Genet 2013, 22:2273-2282.
  • [58]Pekarsky Y, Zanesi N, Aqeilan RI, Croce CM: Animal models for chronic lymphocytic leukemia. J Cell Biochem 2007, 100:1109-1118.
  • [59]ter Brugge PJ, Ta VB, de Bruijn MJ, Keijzers G, Maas A, van Gent DC, Hendriks RW: A mouse model for chronic lymphocytic leukemia based on expression of the SV40 large T antigen. Blood 2009, 114:119-127.
  • [60]Bertilaccio MT, Scielzo C, Simonetti G, Hacken ET, Apollonio B, Ghia P, Caligaris-Cappio F: Xenograft models of chronic lymphocytic leukemia: problems, pitfalls and future directions. Leukemia 2012, 27:534-540.
  • [61]Bonnal S, Vigevani L, Valcarcel J: The spliceosome as a target of novel antitumour drugs. Nat Rev Drug Discov 2012, 11:847-859.
  • [62]Mansouri L, Cahill N, Gunnarsson R, Smedby KE, Tjonnfjord E, Hjalgrim H, Juliusson G, Geisler C, Rosenquist R: NOTCH1 and SF3B1 mutations can be added to the hierarchical prognostic classification in chronic lymphocytic leukemia. Leukemia 2012, 27:512-514.
  • [63]Jeromin S, Haferlach C, Bayer K, Dicker F, Weissmann S, Grossmann V, Alpermann T, Kohlmann A, Haferlach T, Kern W, Schnittger S: SF3B1 mutations have adverse impact on time to treatment especially in patients with 13q deletions: a study on 1,124 chronic lymphocytic leukemia (CLL) patients. In In 54th ASH Annual Meeting and Exposition: December 8-11, 2012.. Atlanta, GA; 2012. abstract 709
  • [64]Stilgenbauer S, Busch R, Schnaiter A, Paschka P, Rossi M, Döhner K, Zenz T, Bühler A, Winkler D, Edelmann J, Mertens D, Bullinger L, Kless S, Mack S, Böttcher S, Ritgen M, Kneba M, Jäger U, Lichter P, Patten N, Wenger MK, Mendila M, Fingerle-Rowson G, Cazzola M, Wendtner C, Fink AM, Fischer K, Hallek M, Döhner H: Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. In 54th ASH Annual Meeting and Exposition: December 8-11, 2012.. Atlanta, GA; 2012. abstract 433
  • [65]Oscier DG, Rose-Zerilli MJ, Winkelmann N, Gonzalez De Castro D, Gomez B, Forster J, Parker H, Parker A, Gardiner A, Collins A, Else M, Cross NC, Catovsky D, Strefford JC: The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood 2013, 121:468-475.
  • [66]Sandmann T, Boutros M: Screens, maps & networks: from genome sequences to personalized medicine. Curr Opin Genet Dev 2012, 22:36-44.
  • [67]Beckman RA, Schemmann GS, Yeang CH: Impact of genetic dynamics and single-cell heterogeneity on development of nonstandard personalized medicine strategies for cancer. Proc Natl Acad Sci U S A 2012, 109:14586-14591.
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